Sex-specific impact of severe obesity in the outcomes of hospitalized patients with COVID-19: a large retrospective study from the Bronx,New York

It has been demonstrated that obesity is an independent risk factor for worse outcomes in patients with COVID-19. Our objectives were to investigate which classes of obesity are associated with higher in-hospital mortality and to assess the association between obesity and systemic inflammation. This was a retrospective study which included consecutive hospitalized patients with COVID-19 in a tertiary center. Three thousand five hundred thirty patients were included in this analysis (female sex: 1579, median age: 65 years). The median body mass index (BMI) was 28.8 kg/m². In the overall cohort, a J-shaped association between BMI and in-hospital mortality was depicted. In the subgroup of men, BMI 35–39.9 kg/m² and BMI ≥40 kg/m² were found to have significant association with higher in-hospital mortality, while only BMI ≥40 kg/m² was found significant in the subgroup of women. No significant association between BMI and IL-6 was noted. Obesity classes II and III in men and obesity class III in women were independently associated with higher in-hospital mortality in patients with COVID-19. The male population with severe obesity was the one that mainly drove this association. No significant association between BMI and IL-6 was noted.

     

Cancer-related neuropathic pain in out-patient oncology clinics: a European survey

Background

Although pain is frequently experienced by patients with cancer, it remains under-treated. The primary aim of this study was to estimate the prevalence of cancer-related neuropathic pain (CRNP) in patients with chronic pain who attended an outpatient clinic for standard care in Europe (irrespective of the reason or stage of the cancer). The secondary aims of this study were to characterise pain and cancer in patients with CRNP (including treatment) and to evaluate the usefulness of the painDETECT (PD-Q) screening tool to help physicians identify a potential neuropathic component of cancer-related pain.

Methods

An observational, non-interventional, cross-sectional, multi-centre study of adult patients with cancer using patient and physician case report forms (CRFs). Patients with CRNP were identified by physicians’ clinical assessments after examining the completed PD-Q.

Results

A total of 951 patients visiting outpatient clinics across Europe were enrolled in this study between August 2010 and July 2011. Of these, 310 patients (32.60%; 95% confidence interval 29.62, 35.58) were identified as having CRNP. Twenty-nine of 39 (74.4%) physicians who completed the CRF relating to the PD-Q considered it a useful tool to help detect CRNP in daily practice and 28 of 39 (71.8%) indicated that they would use this tool in the future for most or some of their patients. Data from physicians before and after review of the completed PD-Qs showed a shift in clinical opinion (either to positive CRNP diagnosis [yes] or negative CRNP diagnosis [no]) in respect of 142 patients; about half of which (74) were categorised with an initial diagnosis of unknown. Opinions also shifted from a no to a yes diagnosis in 10 patients and from a yes to a no diagnosis in 51 patients.

Conclusions

Approximately one-third of adults with cancer experiencing chronic pain attending outpatient clinics as part of routine care were considered to have CRNP in the opinion of the physicians after considering scores on the PD-Q. While physicians did not consider the PD-Q to be a useful tool for all patients, shifts in diagnosis before and after the use of this tool indicate that it may help physicians identify CRNP, especially where there is initial uncertainty.

     

BH3 mimetics and multi-kinase inhibition in AML

In this issue of Blood, Rahmani et al show in preclinical studies that the combination of the multi-kinase inhibitor sorafenib with the BH3 mimetic obatoclax results in enhanced antileukemic effects compared with the effects of each agent alone. This work has important clinical implications because it describes a novel approach to overcome acute myeloid leukemia (AML) cell resistance by combining agents that are currently being investigated in trials as single agents.     

Defining Treatment and Outcomes of Hepaticojejunostomy Failure Following Pancreaticoduodenectomy

Background

The overall complication rate after pancreaticoduodenectomy (PD) approaches 50 %, with anastomotic failure being the most frequent cause of serious postoperative morbidity. Hepaticojejunostomy leaks (also called bile leaks) are the second most common type of leak, behind pancreaticojejunostomy leaks, yet have been the focus of only a single study as reported by Suzuki et al. (Hepatogastroenterology 50:254–257, 12).

Methods

We reviewed the recent experience with bile leaks at a single, high-volume pancreatic surgery center over a six-year time period.

Results

Bile leaks were identified in 16 out of 715 patients (2.2 %). Low preoperative albumin was associated with an increased risk. Bile leaks typically manifested within the first week after surgery as bilious drainage in a surgically placed drain. Associated warning signs included fever and leukocytosis. Patients with a bile leak frequently developed other complications, including a pancreatic fistula, wound infection, delayed gastric emptying, and sepsis. The impact on perioperative outcomes was comparable to patients with a pancreatic leak. A grading system is proposed based on the International Study Group on Pancreatic Fistula model. Grade A bile leaks were classified as those managed with prolonged drainage by operatively placed drains, grade B bile leaks with percutaneous abdominal drainage, and grade C bile leaks with insertion of a percutaneous transhepatic biliary drainage.

Conclusions

Hepaticojejunostomy leaks are rare after PD. The complication severity ranges from trivial to life threatening and is comparable overall to pancreaticojejunostomy leaks. Surgical intervention is rarely, if ever, required. With prompt and aggressive management, a full recovery can be expected.     

Preoperative Imaging for Resectable Periampullary Cancer: Clinicopathologic Implications of Reported Radiographic Findings

Background

High-resolution, multiphase, computed tomography (CT) is a standard preoperative test prior to pancreatectomy, yet the clinical significance of routinely reported findings remains unknown.

Methods

We identified patients who underwent a pancreaticoduodenectomy for a periampullary adenocarcinoma (PA) over the previous 5 years and had a pancreas protocol CT at our institution. Clinicopathologic implications of reported CT findings were evaluated.

Results

There were 155 pancreatic ductal adenocarcinomas (PDA) and 47 non-pancreatic PAs. No mass was visualized on CT in 6 % of PDAs and 23 % of non-pancreatic PA. A size discrepancy of ≥1 cm between radiographic and pathologic tumor diameters was observed in 40 % of PAs, with CT underestimating the size in most instances (75 %). Radiographically enlarged lymph nodes were not associated with true lymph node metastases in PDAs (70 % lymph node positive cases were enlarged on CT vs 74 % lymph node negative, p = 0.5), but were associated with a preoperatively placed biliary endoprosthesis (63 % with endoprosthesis were enlarged vs 37 % no endoprosthesis, p = 0.013). Major visceral vessel involvement on CT was not associated with a vascular resection (3 % with CT vessel involvement vs 2 % without, p = 0.8) or a positive uncinate resection margin (24 vs 20 %, respectively, p = 0.6).

Discussion

While dedicated pancreas protocol CT provides unprecedented detail, the test may lead to overinterpretation of the extent of disease in some instances. A radiographic suggestion of enlarged lymph nodes and vascular involvement does not necessarily preclude exploration with curative intent. CTs with local disease should be reported in an objective template and carefully reviewed by a multidisciplinary group of surgeons, radiologists, and oncologists to avoid missing an opportunity for neoadjuvant therapy or cure by resection.     

Novel approaches to develop community-built biological network models for potential drug discovery

Introduction: Hundreds of thousands of data points are now routinely generated in clinical trials by molecular profiling and NGS technologies. A true translation of this data into knowledge is not possible without analysis and interpretation in a well-defined biology context. Currently, there are many public and commercial pathway tools and network models that can facilitate such analysis. At the same time, insights and knowledge that can be gained is highly dependent on the underlying biological content of these resources. Crowdsourcing can be employed to guarantee the accuracy and transparency of the biological content underlining the tools used to interpret rich molecular data.

Areas covered: In this review, the authors describe crowdsourcing in drug discovery. The focal point is the efforts that have successfully used the crowdsourcing approach to verify and augment pathway tools and biological network models. Technologies that enable the building of biological networks with the community are also described.

Expert opinion: A crowd of experts can be leveraged for the entire development process of biological network models, from ontologies to the evaluation of their mechanistic completeness. The ultimate goal is to facilitate biomarker discovery and personalized medicine by mechanistically explaining patients’ differences with respect to disease prevention, diagnosis, and therapy outcome.