Peripheral inflammation associated with depression and reduced weight loss: a longitudinal study of bariatric patients.

BACKGROUND: Research implicates inflammation in the vicious cycle between depression and obesity, yet few longitudinal studies exist. The rapid weight loss induced by bariatric surgery is known to improve depressive symptoms dramatically, but preoperative depression diagnosis may also increase the risk for poor weight loss. Therefore, we investigated longitudinal associations between depression and inflammatory markers and their effect on weight loss and clinical outcomes in bariatric patients. METHODS: This longitudinal observational study of 85 patients with obesity undergoing bariatric surgery included 41 cases with depression and 44 controls. Before and 6 months after surgery, we assessed depression by clinical interview and measured serum high-sensitivity C-reactive protein (hsCRP) and inflammatory cytokines, including interleukin (IL)-6 and IL-10. RESULTS: Before surgery, depression diagnosis was associated with significantly higher serum hsCRP, IL-6, and IL-6/10 ratio levels after controlling for confounders. Six months after surgery, patients with pre-existing depression still had significantly higher inflammation despite demonstrating similar weight loss to controls. Hierarchical regression showed higher baseline hsCRP levels predicted poorer weight loss (ß = -0.28, p = 0.01) but had no effect on depression severity at follow-up (ß = -0.02, p = 0.9). Instead, more severe baseline depressive symptoms and childhood emotional abuse predicted greater depression severity after surgery (ß = 0.81, p < 0.001; and ß = 0.31, p = 0.001, respectively). CONCLUSIONS: Depression was significantly associated with higher inflammation beyond the effect of obesity and other confounders. Higher inflammation at baseline predicted poorer weight loss 6 months after surgery, regardless of depression diagnosis. Increased inflammation, rather than depression, may drive poor weight loss outcomes among bariatric patients.

Novel JAK2 Exon 14 Mutations L611S or N622Y in cis with JAK2V617F Are Associated with Distinct Clinical Phenotype of Polycythemia Vera and Concurrent Eosinophilia.

Eosinophilic phenotypes in polycythemia vera (PV) and essential thrombocythemia (ET) are rare and poorly characterized. Co-occurring JAK2 mutations in cis, specifically L611S or N622Y mutations, appear to result in a more aggressive clinical phenotype. PV/ET with eosinophilic phenotypes may require full next-generation sequencing to capture co-occurring mutations as opposed to more prevalent single-gene assays. These eosinophilic phenotypes are highly thrombotic and systemic symptoms appear responsive to early use of the janus kinase inhibitor ruxolitinib.

Second-line treatment with CAR T-cell therapy for large B-cell lymphoma.

The landscape for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) has continued to evolve. However, challenges continue to exist, particularly in patients who do not respond to first-line anti-CD20 monoclonal antibody and anthracycline-based therapy or those who experience early relapse. In such patients, the treatment paradigm has changed little in the past 2 decades, with salvage chemotherapy followed by myeloablative chemotherapy and autologous hematopoietic stem cell transplant resulting in historical durable response rates of approximately 40%. Given the success of chimeric antigen receptor (CAR) T-cell therapy in the third- or later-line in the R/R LBCL setting, 3 recent clinical trials (ZUMA-7, BELINDA, and TRANSFORM) have sought to address the clinical need for improved therapies in the high-risk second-line setting for primary R/R disease in the first 12 months. In this review, we analyze these 3 pivotal trials with a focus on clinical trial design, CAR T-cell product attributes, efficacy data, safety data, and patient-reported outcomes when compared with standard of care.

Taking a BiTE out of the CAR T space race.

Chimaeric antigen receptor T-cell (CAR T) therapy has evolved at an exponential pace and seeks to revolutionize the CAR T space with next-generation CARs and expanding indications in plasma cell dyscrasias. Recent developments in Bispecific T-cell engager therapy (BiTEs) may level the playing field with CAR T therapy, offering key advantages with off-the-shelf or on-demand treatment and a manageable toxicity profile to encompass a wider pool of eligible patients in the outpatient setting. The coexistence of both modalities will remain important in overall management and accelerate the next iteration of both cellular and BiTEs. This article summarises the current progress, potential future of both therapies for haematologic malignancies, and their economic implications on the healthcare system.

Peripheral blood blast rate of clearance is an independent predictor of clinical response and outcomes in acute myeloid leukaemia.

The day 14 bone marrow aspirate and biopsy (D14BM) is regularly used to predict achievement of complete remission (CR) with induction chemotherapy in acute myeloid leukemia (AML), however its utility has been questioned. Clearance of peripheral blood blasts (PBB) may serve as an early measure of chemosensitivity. PBB rate of clearance (PBB-RC) was calculated for treatment-naive AML patients (n = 164) undergoing induction with an anthracycline and cytarabine (7+3) and with detectable PBB at diagnosis. PBB-RC was defined as the percentage of the absolute PBB count on the day of diagnosis that was cleared with each day of therapy, on average, until D14 or day of PBB clearance. Each 5% increase in PBB-RC approximately doubled the likelihood of D14BM clearance (OR = 1·81; 95% CI: 1·24-2·64, P < 0·005). PBB-RC was also associated with improved CR rates (OR per 5% = 1·97; 95% CI: 1·27-3·01, P < 0·005) and overall survival (OS) [hazard ratio (HR) per 5% = 0·67; 95% CI: 0·52-0·87]. African American patients had poorer OS adjusted for PBB-RC (HR = 2·18; 95% CI: 1·13-4·23), while race was not associated with D14BM or CR rate. PBB-RC during induction chemotherapy is predictive of D14BM clearance, CR, and OS, and can therefore serve as a prognostic marker for clinical outcomes in AML.

Diagnostic performance of EUS in non-jaundiced patients with an incidental finding of double duct sign on cross-sectional imaging: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Dilatation of the pancreatic duct and common bile duct, known as double duct sign (DDS), suggests sinister pathology at the periampullary region. Non-jaundiced patients with incidental DDS and otherwise normal cross-sectional imaging present a diagnostic dilemma to the multidisciplinary team (MDT). The primary aim of this review was to assess the diagnostic yield of endoscopic ultrasound (EUS) in detecting causal pathology in this patient population. METHODS: A systematic literature search (Medline, EMBASE, Google Scholar, Cochrane database and PROSPERO) was performed to identify original studies that reported EUS findings in patients with incidental DDS. Primary outcome was detection of a periampullary tumour. Secondary outcome was detection of benign causal pathology. Meta-analysis was used to calculate an absolute measure (pooled proportion) of pathology detection. RESULTS: Four studies (177 patients) were included. EUS detection rate for a periampullary tumour was 5% (95% CI, 0-10%) including both adenocarcinomas and adenomas. EUS detection rate for benign causal pathology was 22% (95% CI, 10-34%), the most common being chronic pancreatitis CONCLUSION: Non-jaundiced patients with incidental DDS on cross-sectional imaging have a 5% risk of a periampullary tumour that can be detected by EUS.

Decreased Bleeding Incidence with Direct Oral Anticoagulants Compared to Vitamin K Antagonist and Low-Molecular-Weight Heparin in Patients with Sickle Cell Disease and Venous Thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is a recognized complication of sickle cell disease (SCD), yet the optimal pharmacologic anticoagulant is unknown. METHODS: A retrospective single-institution cohort study of patients with SCD complicated by first VTE from January 2009 through July 2017 was performed using ICD 9/10 codes. Data collected included the anticoagulant used, VTE recurrence, and incidence of bleeding. RESULTS: 109 patients with VTE were identified. SCD genotypes included HbSS in 92 (84%), HbSC in 13 (12%), and HbS-ß+ thalassemia in 4 (4%). After the initial VTE event, 32 patients received a vitamin K antagonist (VKA), 34 for low-molecular-weight heparin (LMWH), and 43 for direct oral anticoagulants (DOACs). 16 patients (15%) experienced a clinically significant bleeding event, including 9 on VKA, 5 on LMWH, and 2 on DOACs. At a median follow-up of 11.8 (range, 3.4-60) months, 33 patients had a recurrent VTE, including 10 on VKA, 10 on LMWH, and 13 on DOACs (p = 0.833). Bleeding incidence was least with the DOACs, which were associated with fewer bleeding events (OR 0.22), and greatest with VKA (OR 1.55) (p < 0.05). CONCLUSION: There was no difference between VTE recurrence and choice of anticoagulation in SCD patients with VTE. Bleeding events were lower for DOACs compared to VKA or LMWH.

Spleen-preserving distal pancreatectomy with and without splenic vessel ligation: a systematic review.

BACKGROUND: Splenic preservation during a distal pancreatectomy (SPDP) may be performed with splenic vessel ligation, known as Warshaw's Technique (WT) or splenic vessel preservation (SVP). The consensus on which approach is best is divided. A systematic review of evidence in the literature was undertaken with the aim of analysing the merits and disadvantages of both WT and SVP. METHODS: A systematic search of medical literature from 1985-2011 was undertaken to identify all comparative studies and case series on SPDP. Non-English papers, series with < 5 patients, technical reports and reviews were excluded. The remaining articles were reviewed considering the study design, surgical technique, outcomes and complications. RESULTS: In 23 relevant studies, 356 patients underwent WT and 572 underwent SVP. In WT patients, the mean operating time (160 versus 215 min, P < 0.001), mean estimated blood loss (301 versus 390 ml, P < 0.001) and length of stay (8 versus 11 days, P < 0.001) was significantly less than the SVP patients, respectively. Considering complications, splenic infarction and splenectomy occurred more frequently in WT patients (P < 0.05). DISCUSSION: WT is technically easier to perform than SVP but has a higher incidence of subsequent splenectomies. Surgeons should be able to perform both procedures and tailor the technique according to the patient.

Parkinson's Disease Diagnosis beyond Clinical Features: A Bio-marker using Topological Machine Learning of Resting-state Functional Magnetic Resonance Imaging.

Parkinson's disease (PD) is one of the leading causes of neurological disability, and its prevalence is expected to increase rapidly in the following few decades. PD diagnosis heavily depends on clinical features using the patient's symptoms. Therefore, an accurate, robust, and non-invasive bio-marker is of critical clinical importance for PD. This study proposes to develop a new bio-marker for PD diagnosis using resting-state functional Magnetic Resonance Imaging (rs-fMRI). Unlike most existing rs-fMRI data analytics using correlational analysis, a Topological Machine Learning approach is proposed to construct the bio-marker. The default functional network is identified first using rs-fMRI. Next, rs-fMRI's high dimensional spatial-temporal data structure is mapped on a Riemann Manifold using topological dimensional reduction. Following the topological dimensional reduction, machine learning is used for classification and sensitivity analysis. The proposed methodology is applied to three open fMRI databases for demonstration and validation. The PD diagnosis accuracy can reach 96.4% when the proposed methodology is used. Thus, rs-fMRI and topological machine learning provide a quantifiable and verifiable bio-marker for future PD early detection and treatment evaluation.

Role of Ursodeoxycholic Acid in the Prevention of Gallstones Formation in Bariatric Patients-a Systematic Review and Meta-Analysis of Randomised Trials.

The aim of this meta-analysis was to assess whether treatment with ursodeoxycholic acid (UDCA) in patients who have undergone bariatric surgery reduces gallstone formation. A systematic literature search was performed using electronic databases (MEDLINE, Embase, CENTRAL, Web of Science, PROSPERO, Google Scholar and the WHO International Clinical Trials Registry platform). RCTs without restrictions on study language, year, status of publication and patient's age were used. Pooled risk ratios were calculated using a random-effects model. Subgroup analyses for drug dose, duration and procedure types were performed. Sensitivity analyses and a summary of findings table were generated to assess the robustness and the level of evidence provided, respectively. Fourteen trials were included (3619 patients, 2292 in UDCA vs 1327 in control group). Procedures included SG, RYGB, OAGB, AGB and Gastroplasty. UDCA dose ranged from 300 to 1200 mg per day. Gallstone formation occurred in 19.3% (8.3% in UDCA vs 38.1% in the control group). UDCA significantly reduced the risk of gallstone formation (14 trials, 3619 patients; RR 0.27, 95% CI 0.18-0.41; P < 0.001). UDCA significantly reduced the risk of symptomatic gallstone disease (6 trials, 2458 patients; RR 0.30, 95% CI 0.21-0.43; P < 0.001). No subgroup difference was found for different doses, duration and type of procedure performed. Oral UDCA treatment significantly reduces the risks of developing gallstones in postoperative bariatric patients from 38 to 8%. The use of 500 to 600 mg UDCA for 6 months is effective and should be implemented in all patients post-bariatric surgery.

The efficacy of GLP-1RAs for the management of postprandial hypoglycemia following bariatric surgery: a systematic review.

OBJECTIVE: Postprandial hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass and gastric sleeve surgery that may detrimentally affect patient quality of life. One likely causal factor is glucagon-like peptide-1 (GLP-1), which has an exaggerated rise following ingestion of carbohydrates after bariatric surgery. This paper sought to assess the role of GLP-1 receptor agonists (GLP-1RAs) in managing postprandial hypoglycemia following bariatric surgery. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus were systematically and critically appraised for all peer-reviewed publications that suitably fulfilled the inclusion criteria established a priori. This systematic review was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P). It followed methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions and is registered with PROSPERO (International Prospective Register of Systematic Reviews; identifier CRD420212716429). RESULTS AND CONCLUSIONS: Postprandial hyperinsulinemic hypoglycemia remains a notoriously difficult to manage metabolic complication of bariatric surgery. This first, to the authors' knowledge, systematic review presents evidence suggesting that use of GLP-1RAs does not lead to an increase of hypoglycemic episodes, and, although this approach may appear counterintuitive, the findings suggest that GLP-1RAs could reduce the number of postprandial hypoglycemic episodes and improve glycemic variability.

Patient-specific comorbidities as prognostic variables for survival in myelofibrosis.

Treatment decisions in primary myelofibrosis (PMF) are guided by numerous prognostic systems. Patient-specific comorbidities have influence on treatment-related survival and are considered in clinical contexts but have not been routinely incorporated into current prognostic models. We hypothesized that patient-specific comorbidities would inform prognosis and could be incorporated into a quantitative score. All patients with PMF or secondary myelofibrosis with available DNA and comprehensive electronic health record (EHR) data treated at Vanderbilt University Medical Center between 1995 and 2016 were identified within Vanderbilt's Synthetic Derivative and BioVU Biobank. We recapitulated established PMF risk scores (eg, Dynamic International Prognostic Scoring System [DIPSS], DIPSS plus, Genetics-Based Prognostic Scoring System, Mutation-Enhanced International Prognostic Scoring System 70+) and comorbidities through EHR chart extraction and next-generation sequencing on biobanked peripheral blood DNA. The impact of comorbidities was assessed via DIPSS-adjusted overall survival using Bonferroni correction. Comorbidities associated with inferior survival include renal failure/dysfunction (hazard ratio [HR], 4.3; 95% confidence interval [95% CI], 2.1-8.9; P = .0001), intracranial hemorrhage (HR, 28.7; 95% CI, 7.0-116.8; P = 2.83e-06), invasive fungal infection (HR, 41.2; 95% CI, 7.2-235.2; P = 2.90e-05), and chronic encephalopathy (HR, 15.1; 95% CI, 3.8-59.4; P = .0001). The extended DIPSS model including all 4 significant comorbidities showed a significantly higher discriminating power (C-index 0.81; 95% CI, 0.78-0.84) than the original DIPSS model (C-index 0.73; 95% CI, 0.70-0.77). In summary, we repurposed an institutional biobank to identify and risk-classify an uncommon hematologic malignancy by established (eg, DIPSS) and other clinical and pathologic factors (eg, comorbidities) in an unbiased fashion. The inclusion of comorbidities into risk evaluation may augment prognostic capability of future genetics-based scoring systems.

CT interpretation in a telestroke network: agreement among a spoke radiologist, hub vascular neurologist, and hub neuroradiologist.

BACKGROUND AND PURPOSE: The American Stroke Association guidelines emphasized the need for further high-quality studies that assess agreement by radiologists and nonradiologists engaged in emergency telestroke assessments and decision-making. Therefore, the objective of this study was to determine the level of agreement of baseline brain CT scan interpretations of patients with acute stroke presenting to telestroke spoke hospitals between central reading committee neuroradiologists and each of 2 groups, spoke hospital radiologists and hub hospital vascular neurologists (telestrokologists). METHODS: The Stroke Team Remote Evaluation Using a Digital Observation Camera Arizona trial was a prospective, urban single-hub, rural 2-spoke, randomized, blinded, controlled trial of a 2-way, site-independent, audiovisual telemedicine and teleradiology system designed for remote evaluation of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis. In the telemedicine arm, the subjects' CT scans were interpreted by the hub telestrokologist and in the telephone arm by the spoke radiologist. All subjects' CT scans were subsequently interpreted centrally, independently, and blindly by 2 hub neuroradiologists. The primary CT outcome was determination of a CT-based contraindication to thrombolytic treatment. Kappa statistics and exact agreement rates were used to analyze interobserver agreement. RESULTS: Fifty-four subjects underwent random assignment. The overall agreement for the presence of radiological contraindications to thrombolysis was excellent (0.91) and did not differ substantially between the hub telestrokologist to neuroradiologist and spoke radiologist to neuroradiologist (0.92 and 0.89, respectively). CONCLUSIONS: In the context of a telestroke network designed to assess patients with acute stroke syndromes, agreement over the presence or absence of radiological contraindications to thrombolysis was excellent whether the comparisons were between a telestrokologist and neuroradiologist or between spoke radiologist and neuroradiologist. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00623350.

Successful endoscopic management of Bouveret syndrome.

We present a frail 83-year-old female with Bouveret syndrome managed using an endoscopic approach. Our patient attended the emergency department with abdominal pain, vomiting and signs of sepsis. She had a recent admission with acute cholecystitis that which had been managed conservatively. Axial imaging revealed aerobilia with a 14 mm common bile duct and a 3.5 cm calculus impacted in the duodenum, in association with a cholecysto-duodenal fistula. After resuscitation, an oesphagoduodenoscopy was performed under general anaesthesia. The large stone was seen impacted in the first part of duodenum. Mechanical lithotripsy and the Kudo snare were employed to fragment the stone and remove large fragments. Bouveret syndrome is rarely managed with success through endoscopy. The syndrome typically occurs in frail, elderly co-morbid patients who would benefit from endoscopic management over open surgery. Despite low success rates historically, endoscopic management is a reasonable and viable option in cases of Bouveret syndrome.

Liver abscess secondary to fishbone ingestion: case report and review of the literature.

We report a rare silent migration of a fishbone into the liver and review the relevant literature. A 56-year-old man presented with a 2-day history of dull epigastric pain and raised inflammatory markers. Computerized tomography scan revealed a 4-cm abscess in the left lobe of the liver, with a linear radio-dense foreign body within the collection. At laparoscopy the hepatogastric fistula was disconnected. The fishbone was retrieved from the liver. Gastrostomy was closed with an omental patch. The patient had an uneventful recovery. Fifty-two cases of liver abscess secondary to enterohepatic fishbone migration were reported with over two-thirds presenting with a left-lobe abscess. There was marked variability in the management of liver abscess in the setting of fishbone migration-summarized in table. We believe that laparoscopic drainage of the abscess and extraction of the foreign body offer control of the source of sepsis and diminishes recurrence, whilst having a low-risk profile.

Effect of the learning curve on survival after laparoscopic liver resection for colorectal metastases.

BACKGROUND: Laparoscopic liver resection (LLR) is a highly demanding procedure with great variability. Previously published randomized trials have proven oncological safety of laparoscopic liver resection (LLR) as compared to open surgery. However, these were started after the learning curve (LC) was established. This leaves the question of whether the LC of LLR in the early laparoscopic era has affected the survival of patients with colorectal liver metastasis (CRLM). METHODS: All consecutive LLRs performed by a single surgeon between 2000 and 2019 were retrospectively analysed. A risk-adjusted cumulative sum (RA-CUSUM) chart for conversion rate and the log regression analysis of the blood loss identified two phases in the LC. This was then applied to patients with CRLM, and the two subgroups were compared for recurrence-free (RFS) and overall survival (OS). The analysis was repeated with propensity score-matched (PSM) groups. RESULTS: A total of 286 patients were included in the LC analysis, which identified two distinct phases, the early (EP; 68 patients) and the late (LP; 218 patients) phases. The LC was applied to 192 patients with colorectal liver metastasis (EPc, 45 patients; LPc, 147 patients). For patients with CRLM, R0 resection was achieved in 93 per cent: 100 per cent in the EPc group and 90 per cent in the LPc group (P = 0.026). Median OS and RFS were 60 and 16 months, respectively. The 5-year OS and RFS were 51 per cent and 32.7 per cent, respectively. OS (hazard ratio (h.r.) 0.78, 95 per cent confidence interval (c.i.) 0.51 to 1.2; P = 0.286) and RFS (h.r. 0.94, 95 per cent c.i. 0.64 to 1.37; P = 0.760) were not compromised by the learning curve. The results were replicated after PSM. CONCLUSION: In our experience, the development of a laparoscopic liver resection programme can be achieved without adverse effects on the long-term survival of patients with CRLM.

Reduction in the Prevalence of Thrombotic Events in Sickle Cell Disease after Allogeneic Hematopoietic Transplantation.

Thrombosis is a recognized complication in sickle cell disease (SCD). Allogeneic hematopoietic cell transplantation (allo-HCT) remains the sole curative option for patients with severe SCD phenotypes. Data describing the effects of allo-HCT on recurrent thrombotic events (venous and arterial events) are limited, however. We evaluated 31 patients with SCD who underwent allo-HCT with a median follow-up of 34.5 months (range, 13 to 115) post-transplantation. No patient continued anticoagulation or antiplatelet therapy after allo-HCT. There was an absolute difference of 32% (95% confidence interval [CI], 12.3% to 32.2%; P = .002) in the prevalence of venous thromboembolic (VTE) events before and after allo-HSCT. In addition, there was an absolute difference of 38.5% (95% CI, 10.63 to 45.96; P = .006) in the number of ischemic cerebrovascular accidents (CVAs) occurring before and after allo-HSCT. Patients with severe SCD who undergo allo-HCT are less likely to develop recurrent thrombotic events compared with a control cohort of patients matched for age and genotype (odds ratio, 0.22; 95% CI, 0.058 to 0.83; P = .025). Following curative therapy with allo-HCT, there is a reduction in recurrent arterial and venous thrombosis in patients with severe SCD phenotypes.

Fundus-first transumbilical single-incision laparoscopic cholecystectomy with a cholangiogram: a feasibility study.

BACKGROUND: An increasing number of techniques are emerging in the literature describing single-incision laparoscopic cholecystectomy (SILC). The advent of a new surgical approach is a reminder of the increase in bile duct injuries in the past when laparoscopic cholecystectomy was first introduced. With this in mind, the authors describe a safe and reproducible approach to SILC. METHODS: Between August 2008 and August 2009, 20 patients with symptomatic gallbladder disease underwent SILC using a totally transumbilical fundus-first approach with an intraoperative cholangiogram. Data including pain scores were collected prospectively. RESULTS: In this initial series, the median operative time was 103 min (range, 55-177 min), including the time for two patients undergoing additional procedures at the time of surgery. Intraoperative cholangiograms were completed for 18 of 19 patients. Additional ports were required in four patients for safe completion of the procedure. The mean pain score 12 h postoperatively was 2.5 on a visual analogue scale with a range of 0-10. There was no morbidity or mortality. CONCLUSION: According to the findings, SILC with an intraoperative cholangiogram can be performed safely using a fundus-first approach. However, for SILC to become the operation of choice for the treatment of gallbladder disease, evidence is required to demonstrate its advantage over laparoscopic cholecystectomy.