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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.

The coronavirus disease 2019 pandemic is wreaking havoc on society, especially health-care systems, including disrupting bariatric and metabolic surgery. The current limitations on accessibility to non-urgent care undermine postoperative monitoring of patients who have undergone such operations. Furthermore, like most elective surgery, new bariatric and metabolic procedures are being postponed worldwide during the pandemic. When the outbreak abates, a backlog of people seeking these operations will exist. Hence, surgical candidates face prolonged delays of beneficial treatment. Because of the progressive nature of obesity and diabetes, delaying surgery increases risks for morbidity and mortality, thus requiring strategies to mitigate harm. The risk of harm, however, varies among patients, depending on the type and severity of their comorbidities. A triaging strategy is therefore needed. The traditional weight-centric patient-selection criteria do not favour cases based on actual clinical needs. In this Personal View, experts from the Diabetes Surgery Summit consensus conference series provide guidance for the management of patients while surgery is delayed and for postoperative surveillance. We also offer a strategy to prioritise bariatric and metabolic surgery candidates on the basis of the diseases that are most likely to be ameliorated postoperatively. Although our system will be particularly germane in the immediate future, it also provides a framework for long-term clinically meaningful prioritisation.

Obesity is a chronic progressive disease that decreases longevity and has associated co-morbidities. Diet, lifestyle and behavioural modifications are essential components in the armamentarium for treating obesity. These alone are, however, not always effective in the long term. Bariatric and metabolic surgery (BMS) safely results in maintained weight loss and amelioration of co-morbidities. This article aims to provide an overview of different BMS procedures, mechanisms of action, outcomes and potential complications.

•A durable reduction in venous and arterial thrombotic events was observed following allogeneic hematopoietic cell transplantation (HCT) in patients with sickle cell disease (SCD).•Post-transplantation thrombotic events were not associated with acute or chronic graft-versus-host disease.•Allogeneic HCT is a validated, curative therapy with the potential to durably reduce venous and arterial thrombotic events in SCD.

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Chest radiographs are complex, heterogeneous medical images that depict many different types of tissues, and many different types of abnormalities. A radiologist develops a sense of what visual textures are typical for each anatomic region within chest radiographs by viewing a large set of "normal" radiographs over a period of years. As a result, an expert radiologist is able to readily detect atypical features. In our previous research, we modeled this type of learning by (1) collecting a large set of "normal" chest radiographs, (2) extracting local textural and contour features from anatomical regions within these radiographs, in the form of high-dimensional feature vectors, (3) using a distance-based transductive machine learning method to learn what it typical for each anatomical region, and (4) computing atypicality scores for the anatomical regions in test radiographs. That research demonstrated that the transductive One-Nearest-Neighbor (1NN) method was effective for identifying atypical regions in chest radiographs. However, the large set of training instances (and the need to compute a distance to each of these instances in a high dimensional space) made the transductive method computationally expensive. This paper discusses a novel online Variance Based Instance Selection (VBIS) method for use with the Nearest Neighbor classifier, that (1) substantially reduced the computational cost of the transductive 1NN method, while maintaining a high level of effectiveness in identifying regions of chest radiographs with atypical content, and (2) allowed the incremental incorporation of training data from new informative chest radiographs as they are encountered in day-to-day clinical work.

Inductive learning refers to machine learning algorithms that learn a model from a set of training data instances. Any test instance is then classified by comparing it to the learned model. When the set of training instances lend themselves well to modeling, the use of a model substantially reduces the computation cost of classification. However, some training data sets are complex, and do not lend themselves well to modeling. Transductive learning refers to machine learning algorithms that classify test instances by comparing them to all of the training instances, without creating an explicit model. This can produce better classification performance, but at a much higher computational cost. Medical images vary greatly across human populations, constituting a data set that does not lend itself well to modeling. Our previous work showed that the wide variations seen across training sets of "normal" chest radiographs make it difficult to successfully classify test radiographs with an inductive (modeling) approach, and that a transductive approach leads to much better performance in detecting atypical regions. The problem with the transductive approach is its high computational cost. This paper develops and demonstrates a novel semi-transductive framework that can address the unique challenges of atypicality detection in chest radiographs. The proposed framework combines the superior performance of transductive methods with the reduced computational cost of inductive methods. Our results show that the proposed semitransductive approach provides both effective and efficient detection of atypical regions within a set of chest radiographs previously labeled by Mayo Clinic expert thoracic radiologists.

Abstract: 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.

Hepatocyte transplantation is dependent on the availability of good quality human hepatocytes isolated from donor liver tissue. Hepatocytes obtained from livers rejected for transplantation on the grounds of steatosis are often of low viability and not suitable for clinical use. The aim of this study was to evaluate the effects of the antioxidant N-acetylcysteine (NAC) on the function of hepatocytes isolated from steatotic donor livers. Human hepatocytes were isolated from 10 severely steatotic (>60%) donor livers rejected for transplantation. The left lateral segment of the donor liver was dissected into two equal size pieces and randomized to NAC or control. NAC (5 mM) was added to the first perfusion buffer of the standard collagenase digestion technique. Cells from tissues perfused with NAC had a significantly higher mean viability (81.1 ± 1.7% vs. 66.0 ± 4.7%; p= 0.003) and cell attachment (1.08 ± 0.26 vs. 0.67 ± 0.18 OD units; p= 0.012). Addition of NAC during isolation of human hepatocytes from steatotic donor liver tissue significantly improved the outcome of cell isolation. Further studies are needed to investigate the mechanism(s) of this effect. Incorporation of NAC in the hepatocyte isolation protocol could increase the availability of hepatocytes for transplantation.

Laparoscopic stapling devices are used widely in laparoscopic surgery, for division of vessels and creation of anastomoses. Their use in the division of a widened cystic duct at laparoscopic cholecystectomy has been reported earlier. We present 3 different complications occurring after division of the cystic duct using the EndoGIA stapling device. A review of the literature has been performed and safe alternative techniques for laparoscopic ligation of the cystic duct are proposed.

Background: Obesity is a major risk factor for the development of endothelial dysfunction. We explored the effect of different degrees of body mass on endothelial function, lipids, systemic inflammation and glucose homeostasis and the effect of surgically-induced weight loss on endothelial function in severely obese humans. Methods: A cross-sectional study of healthy subjects across a wide range of body fatness was performed to characterize the effect of obesity on flow-mediated dilatation (FMD), systemic inflammation, blood pressure and insulin sensitivity. A longitudinal study was performed to assess the effect of bariatric surgery induced weight loss on these parameters. 73 healthy subjects across a wide range of body mass were recruited; of these, 8 underwent bariatric surgery (median BMI 52.2 kg/m2, interquartile range 50.355.9). Endothelial dependent vasodilatation was measured using the brachial artery vasodilatory response to forearm hyperemia assessed using highresolution ultrasonography. Results: Obese subjects were characterised by a complex collection of abnormalities, with hypertension, impaired glucose homeostasis, systemic inflammation and reduced FMD. BMI ≤25 kg/m2 (median FMD 9.7%, interquartile range 6.8-12.2), BMI >30 kg/m2 (median FMD 6.7% 4.8-7.5), P=0.01 comparing FMD in lean and obese subjects. A mean reduction in weight of 23.4 (4.6) kg produced an improvement in FMD from 5.3% (3.87.0) to 10.2% (7.6-13.3), P=0.01. Conclusions: Even moderate obesity leads to endothelial dysfunction. In severely obese subjects, FMD is normalized by weight loss. This improvement in FMD is associated with a decline in inflammatory markers, blood pressure and insulin. The improvement in FMD occurred despite patients remaining significantly obese. These results suggest that an integrated approach to improving endothelial function in obese humans may be necessary.

Background: Obesity surgery has been shown to result not only in sustained weight loss, but also in improvements in psychological morbidity and quality of life. The present study aimed to explore the mechanisms behind the success of surgery and to examine how it might bring about such changes in patients' health status. Methods: Both quantitative and qualitative methods were used. A questionnaire was completed by patients who had undergone bariatric surgery in the past 4 years (n=22) and a matched-group of waiting list controls (n=39). In depth interviews were then carried out with 15 surgical patients. Results: The quantitative study showed that the surgical group weighed less, had more negative experiences of eating and yet reported improved subjective health status using a range of validated tools. The qualitative study provided some insights into this improved health status, with the surgical patients reporting improved energy and self-esteem. The patients also reported a fundamental shift in their relationship with food. In particular, they described changes in their eating behavior and stated that they had a new experience of fullness and a reduction in their hunger. Furthermore, they described how food now had a reduced role in their lives and that the operation had made them feel more in control of their food intake. Conclusion: Post-surgical improvements in health status may not only be a result of the non-specific consequences of surgery brought about by weight loss, but also a result of the specific impact of the surgical procedure itself. By enforcing a reduction in the amount of food that can be eaten, restrictive surgery seems to generate changes in the individuals' relationship to food and may help to re-establish a perception of control over eating behavior.

Background:Pancreatic blood flow is diminished in experimental models of acute and chronic pancreatitis. We attempted to develop a safe and reliable technique for its measurement in patients and to examine blood flow in patients with chronic pancreatitis and in control subjects. Method:Pancreatic blood flow was measured using the hydrogen gas clearance technique and an endoscopically placed platinum ductal electrode. Pancreatic blood flow was measured in 12 patients with chronic pancreatitis diagnosed clinically and radiographically, and in 11 control patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for non-pancreatic pathology. Results:Patients with chronic pancreatitis had a significantly lower pancreatic blood flow compared with control patients (51.5 versus 91.7 mL/min/100 gm, p< 0.01). With secretin stimulation pancreatic blood flow increased in two control patients, whereas this notable rise was not seen in three patients with chronic pancreatitis. Conclusions:Measurement of pancreatic blood flow with an endoscopically placed electrode is relatively safe and simple to perform. The scarring and vascular fibrosis associated histologically with chronic pancreatitis is reflected in lower pancreatic blood flow.

Acute hemorrhage in the course of chronic pancreatitis is the most serious and challenging complication, and its treatment has been the subject of controversy for years. We relate our experience in the management of this complication by superselective microcoil embolization. Five patients with acute hemorrhage resulting from chronic pancreatitis between 1994 and 1997 were included in this study. All patients were men with a median age of 44 years (range, 29–59 years). The bleeding occurred into a pseudocyst in all patients, with the splenic artery as feeding vessel. In all instances, the bleeding was successfully controlled by superselective microcoil embolization. Two patients underwent subsequent uneventful elective pseudocystojejunostomy. There was no mortality or morbidity, and no rebleeding occurred during a median follow-up of 22 months (range, 8-36 months). In appropriate patients, diagnostic angiography and superselective microcoil embolization may obviate the need for emergency surgery and should be considered as treatment alternative.

OBJECTIVE: To compare the short- and long-term morbidity and mortality rates of the standard Whipple pancreatoduodenectomy (SW) and its pylorus-preserving modification (PPW) in patients with malignant periampullary disease. DESIGN: Retrospective medical record review and quality of life assessment by telephone interview. SETTING: University medical center. STUDY PARTICIPANTS: Sixty-seven patients who underwent pancreatoduodenectomy (52 SW and 15 PPW) from June 1988 to January 1994. INTERVENTION: The SW and PPW. MAIN OUTCOME MEASURES: Operative features and short- and long-term complications were analyzed with respect to the type and stage of cancer and the kind of pancreatic resection. Mean follow-up was 32 months (range, 1 to 5 years). RESULTS: The operative mortality rate for all patients who had a pancreatic resection was 1.5%. The diagnoses in the PPW vs SW groups were pancreatic cancer (four vs 27 patients), ampullary cancer (six vs seven patients), duodenal cancer (zero vs six patients), and bile duct cancer (five vs one patient). Operative mortality rates (0% vs 1.55%) and operative times (2 minutes longer for SW) were similar. Delayed gastric emptying (61% vs 41%) was more common in the PPW group, resulting in a longer hospitalization (24 vs 18 days) and a greater cost in the PPW group (P=.04). In the PPW group, a mean of five lymph nodes was removed compared with 10 in the SW group (P=.04). CONCLUSIONS: The data provided no evidence of any advantage for the PPW in patients with malignant periampullary tumors. We continue to advocate the SW for pancreatic cancer.(Arch Surg. 1995;130:838-843)

This report describes 2 heretofore unreported sonographic findings that may aid in the antenatal diagnosis of posterior urethral valves. Each of 2 fetuses showed a prominent or thickened posterior urethra and one or more bright echogenic lines representing valve tissue within a dilated and/or thickened posterior urethra. These findings helped solidify the antenatally suspected diagnosis of posterior urethral valves. The diagnosis was confirmed clinically and surgically during neonatal life. These 2 imaging findings may help in providing a more definitive antenatal diagnosis of posterior urethral valves and allow more expeditious therapy. © 1998 John Wiley & Sons, Inc. J Clin Ultrasound 26:366–370, 1998.

Green: Scripps: Honoraria, Other: travel; North American Thrombosis: Honoraria; CSL: Research Funding; Baxter,: Research Funding; Baxalta: Research Funding; Shire US Inc: Other: clinical trial support. Dholaria:bms: Research Funding; Poseida: Research Funding; Angiocrine: Research Funding; Takeda: Research Funding; J&J: Research Funding.

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).

Tophaceous gout is commonly encountered and is amenable to effective medical management. A rare case of tophaceous gout in a tripartite medial sesamoid bone of the great toe is presented. Clinical presentation, differential diagnosis, and treatment of hallucal sesamoid pain are discussed.

Emadi: NewLink Genetics: Research Funding.

Badros: Karyopharm: Research Funding; Celgene: Consultancy, Research Funding; GSK: Research Funding.

No relevant conflicts of interest to declare.

Abstract: Laparoscopic surgery via a single port is an evolving technique being applied to an increasing variety of operations [1]. Multiple series over the past 3 years have shown single-incision laparoscopic cholecystectomy to be feasible and safe [2]. The ergonomic difficulties of single-port laparoscopy include a loss of instrument triangulation and operation with camera and instruments in parallel. Many different modifications of techniques and equipment have been used to compensate. Single-port techniques have been applied by a few authors to laparoscopic nephrectomy [3], splenectomy [4], and obesity surgery [5, 6]. Laparoscopic liver resection is well established and shown to be safe in multiple series [7]. The laparoscopic approach is accepted as the gold standard for resection of segments 2 and 3 [8]. To the authors’ knowledge, no reports of laparoscopic liver resection via a single port have been published. They report the use of their technique for single-incision laparoscopic left lateral segmentectomy in a patient with a solitary segment 2 colorectal liver metastasis. The authors maintained strict oncologic principles and adhered to their standard laparoscopic technique as far as possible. They used a TriPort (Advanced Surgical Concepts, Wicklow, Ireland) placed via a 12-mm incision at the umbilicus. Following diagnostic laparoscopy and intraoperative liver ultrasound, hepatic attachments were divided using electrocautery. Parenchymal transection and vascular control were achieved using an ultrasonic dissector and laparoscopic staplers. Standard straight laparoscopic instruments were used. A number of technical challenges were apparent. Movement of instruments was jerky at times, either because instruments were clashing with one another other or deflecting the camera. The multiport device can be stiff, requiring copious lubrication throughout surgery. Crossing hands facilitates internal triangulation of the operating instruments to allow retraction or to apply tension, for example, during the division of hepatic attachments. Control of minor hemorrhage is possible with judicious and patient application of pressure using small pieces of surgical gauze. An articulating laparoscopic stapler is useful to achieve the ideal angle of staple deployment during transection of vascular pedicles. The specimen was extracted by extending the umbilical incision. No complications occurred. The patient was able to resume an oral diet and full mobility free of opioid analgesia on the first postoperative day. The resection margin was clear. This video demonstrates that the authors’ technique is feasible and oncologically safe for selected patients requiring liver resection.

Computer Aided Detection (CADe) and Computer Aided Diagnosis (CADx) are relatively recent areas of research that attempt to employ feature extraction, pattern recognition, and machine learning algorithms to aid radiologists in detecting and diagnosing abnormalities in medical images. However, these computational methods are based on the assumption that there are distinct classes of abnormalities, and that each class has some distinguishing features that set it apart from other classes. However, abnormalities in chest radiographs tend to be very heterogeneous. The literature suggests that thoracic (chest) radiologists develop their ability to detect abnormalities by developing a sense of what is normal, so that anything that is abnormal attracts their attention. This paper discusses an approach to CADe that is based on a technique called anomaly detection (which aims to detect outliers in data sets) for the purpose of detecting atypical regions in chest radiographs. However, in order to apply anomaly detection to chest radiographs, it is necessary to develop a basis for extracting features from corresponding anatomical locations in different chest radiographs. This paper proposes a method for doing this, and describes how it can be used to support CADe.