Citations

Abstract The risk of intracranial hemorrhage (ICH) associated with the use of bevacizumab (BEV) has been a topic of several reviews in the literature, and is considered to be a potential adverse effect of BEV when used in patients with malignant glioma. We performed a single-center retrospective chart-review identifying glioma patients treated with BEV at our institution. 595 unique patients who received BEV with documented follow up were identified. Of these patients, 23 (3.9%) developed ICH within 12 weeks (five half-lives) of a BEV infusion (median 9 days post infusion, 1-24 days IQR). There was a trend towards statistical significance between dose administered and the incidence of hemorrhage (P=0.06), with all 23 hemorrhages occurring in patients treated with 10 mg/kg (n=21/490) per infusion or 15 mg/kg per infusion (n=2/35) (n=525, 88.2% of cohort). No patient on dosing regimens of 7.5 mg/kg (n=72) or 5 mg/kg per infusion (n=16) (n=88, 14.7% of cohort) developed ICH. Therapeutic anticoagulation and concomitant BEV therapy was observed in 103 (17%) patients with 10 patients (10/93, 9.7%) developing an ICH (n=10), at a rate significantly higher than in patients treated with bevacizumab alone (13/479, 2.6%) (p=0.0025). When hemorrhages occurred (with or without concomitant anticoagulation) they were associated with high morbidity and mortality (ECOG 3.54 versus 1.26, p = < 0.0001), with 12 patients (52%) suffering severe debility (n=2) or death (n=10). CONCLUSION: Bevacizumab associated intracerebral hemorrhages remain uncommon events, similar to the baseline rate of spontaneous hemorrhage associated with malignant glioma. We observed a trend towards significance with higher doses per infusion associated with an increased rate of intracerebral hemorrhage. The combination of anticoagulation and BEV appears to confer a greater risk of hemorrhage than BEV alone.

AbstractBackgroundWhile parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), liver resection (LR) is increasingly performed with CRS/HIPEC.MethodsPatients from the US HIPEC Collaborative (2000–2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0‐1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival (OS).ResultsA total of 658 patients were included. About 83 (15%) underwent LR of colorectal (58%) or invasive appendiceal (42%) metastases. LR patients had more complications (81% vs. 60%; p = .001), greater number of complications (2.3 vs. 1.5; p < .001) per patient and required more reoperations (22% vs. 11%; p = .007) and readmissions (39% vs. 25%; p = .014) than non‐LR patients. LR patients had decreased OS (2‐year OS 62% vs. 79%, p < .001), even when accounting for peritoneal carcinomatosis index and histology type. Preoperative factors associated with decreased OS on multivariable analysis in LR patients included age < 60 years (HR, 3.61; 95% CI, 1.10–11.81), colorectal histology (HR, 3.84; 95% CI, 1.69–12.65), and multiple liver tumors (HR, 3.45; 95% CI, 1.21–9.85) (all p < .05). When assigning one point for each factor, there was an incremental decrease in 2‐year survival as the risk score increased from 0 to 3 (0: 100%; 1: 91%; 2: 58%; 3: 0%).ConclusionsAs CRS/HIPEC + LR has become more common, we created a simple risk score to stratify patients considered for CRS/HIPEC + LR. These data aid in striking the balance between an increased perioperative complication profile with the potential for improvement in OS.

The first adjunctive hormone therapy for chronic hypoparathyroidism, recombinant human parathyroid hormone (1–84) (rhPTH(1–84)) was approved by the FDA in January 2015. Since the approval of rhPTH(1–84), growing interest has developed in other agents to treat this disorder in both the scientific community and among pharmaceutical companies. For several reasons, conventional therapy with calcium and activated vitamin D supplementation, magnesium supplementation as needed, and occasionally thiazide-type diuretic therapy remains the mainstay of treatment, while endocrinologists and patients are constantly challenged by limitations of conventional treatment. Serum calcium fluctuations, increased urinary calcium, hyperphosphatemia, and a constellation of symptoms that limit mental and physical functioning are frequently associated with conventional therapy. Understanding how conventional treatment and hormone therapy work in terms of pharmacokinetics and pharmacodynamics is key to effectively managing chronic hypoparathyroidism. Multiple questions remain regarding the effectiveness of PTH adjunctive therapy in preventing or slowing the onset and progression of the classical complications of hypoparathyroidism, such as chronic kidney disease, calcium-containing kidney stones, cataracts, or basal ganglia calcification. Several studies point toward an improvement in the quality of life during replacement therapy. This review will discuss current clinical and research challenges posed by treatment of chronic hypoparathyroidism. Key points: Conventional therapy with calcium and activated forms of vitamin D are currently the mainstays of treatment for most patients with chronic hypoparathyroidism. Hormone therapy can be administered through FDA-approved once-daily rhPTH(1–84), or off-label multiple-daily injections of teriparatide. The former is the only FDA-approved drug, with safety and efficacy supported by a randomized placebo-controlled trial and open-label long-term extension trial data. Twice-daily teriparatide has been used in children safely for up to 10 years. New pharmacological options that replace the deficient hormone wi ll likely be available within the next few years.

AbstractThe functional lumen imaging probe (FLIP) is a diagnostic tool that utilizes impedance planimetry to allow the assessment of luminal diameter and distensibility. It has been used primarily in esophageal diseases, in particular, in the assessment of achalasia, esophagogastric junction outflow obstruction, and eosinophilic esophagitis (EoE). The usage and publications have increased over the past decade and it is now an essential tool in the armamentarium of the esophagologist. Indications are emerging outside of the esophagus, in particular with regard to gastroparesis. Our paper will review the history of FLIP, optimal current usage, data for key esophageal disorders (including achalasia, reflux, and EoE), data for nonesophageal disorders, and our sense as to whether FLIP is ready for prime time, as well as gaps in evidence and suggestions for future research.

The functional lumen imaging probe (FLIP) measures luminal dimensions using impedance planimetry, performed most often during sedated upper endoscopy. Mechanical properties of the esophageal wall and opening dynamics of the esophagogastric junction (EGJ) can be objectively evaluated in esophageal motor disorders, eosinophilic esophagitis, esophageal strictures, during esophageal surgery and in postsurgical symptomatic states. Distensibility index, the ratio of EGJ cross sectional area to intraballoon pressure, is the most useful FLIP metric. Secondary peristalsis from balloon distension can be displayed topographically as repetitive anterograde or retrograde contractile activity in the esophageal body, similar to high-resolution manometry. Real-time interpretation and postprocessing of FLIP metadata can complement the identification of esophageal outflow obstruction and achalasia, especially when findings are inconclusive from alternate esophageal tests in symptomatic patients. FLIP can complement the diagnosis of achalasia when manometry and barium studies are inconclusive or negative in patients with typical symptoms. FLIP can direct adequacy of disruption of the EGJ in achalasia when used during and immediately after myotomy and pneumatic dilation. Lumen diameter measured using FLIP in eosinophilic esophagitis and in complex strictures can potentially guide management. An abbreviated modification of the Grading of Recommendations Assessment, Development, and Evaluation was used to determine the quality of available evidence and recommendations regarding FLIP utilization. FLIP metrics that are diagnostic or suggestive of an abnormal motor pattern and metrics that define normal esophageal physiology were developed by consensus and are described in this review.

AbstractBackgroundComprehensive analysis of trauma care between high‐, middle‐, and low‐income countries (HIC/MIC/LIC) is needed to improve global health. Comparison of HIC and MIC outcomes after damage control laparotomy (DCL) for patients is unknown. We evaluated DCL utilization among patients treated at high‐volume trauma centers in the USA and South Africa, an MIC, hypothesizing similar mortality outcomes despite differences in resources and setting.MethodsPost hoc analysis of prospectively collected trauma databases from participating centers was performed. Injury severity, physiologic, operative data and post‐operative outcomes were abstracted. Univariate and multivariable analyses were performed to assess differences between HIC/MIC for the primary outcome of mortality.ResultsThere were 967 HIC and 602 MIC patients who underwent laparotomy. DCL occurred in 144 MIC patients (25%) and 241 HIC (24%) patients. Most sustained (58%) penetrating trauma with higher rates in the MIC compared to the HIC (71 vs. 32%, p = 0.001). Between groups, no differences were found for admission physiology, coagulopathy, or markers of shock except for increased presence of hypotension among patients in the HIC. Crystalloid infusion volumes were greater among MIC patients, and MIC patients received fewer blood products than those in the HIC. Overall mortality was 30% with similar rates between groups (29 in HIC vs. 33% in MIC, p = 0.4). On regression, base excess and penetrating injury were independent predictors of mortality but not patient residential status.ConclusionUse and survival of DCL for patients with severe abdominal trauma was similar between trauma centers in HIC and MIC settings despite increased penetrating trauma and less transfusion in the MIC center. While the results overall suggest no gap in care for patients requiring DCL in this MIC, it highlights improvements that can be made in damage control resuscitation.

ABSTRACT Normocalcemic primary hyperparathyroidism (NHPT) was first described over 10 years ago, but uncertainties still remain about its definition, prevalence, and rates of complications. As a result, consensus management guidelines for this condition have not yet been published. Several hypotheses have been proposed for the pathophysiology of NHPT, but it may be a heterogeneous disorder with multiple causes, rather than a single etiology that explains this biochemical phenotype. A common clinical concern is whether NHPT should be treated surgically when complications are already present at first recognition of the disorder, rather than following patients clinically over time. The literature on NHPT is based mostly on larger studies of population‐based cohorts and smaller studies from referral centers. Lack of rigorous diagnostic criteria and selection bias inherent in populations seen at tertiary referral centers may explain the heterogeneity of reported rates of bone and renal complications in relation to consistently mild laboratory alterations. Unresolved questions remain about the significance of NHPT when it is diagnosed biochemically without evident bone or kidney complications. Moreover, its natural history remains to be elucidated because a proportion of what is classified as NHPT may revert to normal spontaneously, thus revealing previously unrecognized secondary hyperparathyroidism. These issues indicate that caution should be used in recommending surgery for NHPT. This review will focus on recent issues regarding the pathophysiology, evaluation, and management of NHPT. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.