Citations

Case: We present a case of a 71-year-old woman with history of left-sided shoulder arthritis who underwent standard total shoulder arthroplasty using a novel hybrid glenoid component. After 3 years, she sustained traumatic dissociation of the interface between the polyethylene face and central titanium post, a unique failure mechanism of the hybrid glenoid component. This was successfully corrected through conversation to reverse shoulder arthroplasty (RSA). Follow-up after 2 years demonstrated marked improvement in pain and function. Conclusion: Hybrid glenoid components present a unique failure mechanism as compared to traditional glenoid loosening and can be effectively corrected with RSA.

Pancreatic ductal adenocarcinoma is a recalcitrant tumor with minimal response to conventional chemotherapeutic approaches. Oncogenic signaling by activated tyrosine kinases has been implicated in cancers resulting in activation of diverse effector signaling pathways. Thus, the discovery of aberrantly activated tyrosine kinases is of great interest in developing novel therapeutic strategies in the treatment and management of pancreatic cancer. Patient-derived tumor xenografts (PDXs) in mice serve as potentially valuable preclinical models as they maintain the histological and molecular heterogeneity of the original human tumor. Here, we employed high-resolution mass spectrometry combined with immunoaffinity purification using anti-phosphotyrosine antibodies to profile tyrosine phosphoproteome across 13 pancreatic ductal adenocarcinoma PDX models. This analysis resulted in the identification of 1199 tyrosine-phosphorylated sites mapping to 704 proteins. The mass spectrometric analysis revealed widespread and heterogeneous activation of both receptor and non-receptor tyrosine kinases. Preclinical studies confirmed ephrin type-B receptor 4 (EphB4) as a potential therapeutic target based on the efficacy of human serum albumin-conjugated soluble EphB4 in mice bearing orthotopic xenografts. Immunohistochemistry-based validation using tissue microarrays from 346 patients with PDAC showed significant expression of EphB4 in >70% of patients. In summary, we present a comprehensive landscape of tyrosine phosphoproteome with EphB4 as a promising therapeutic target in pancreatic ductal adenocarcinoma.

Background: Obesity paradox is a phenomenon in which obesity increases the risk of obesity-related chronic diseases but paradoxically is associated with improved survival among obese patients with these diagnoses. Objectives: The aim of this study was to explore the obesity paradox among critically ill patients with cirrhosis admitted to the Intensive Care Unit. Methods: A retrospective cohort of 1,143 consecutive patients with cirrhosis admitted to the ICU between January of 2006 and December of 2015 was analyzed. Primary outcome of interest was in-hospital mortality with secondary end points including ICU and short-term mortality at 30 days post ICU admission. Results: Logistic regression with generalized additive models was used, controlling for clinically relevant and statistically significant factors to determine the adjusted relationship between body mass index (BMI) and ICU, post-ICU in-hospital, and 30 day mortality following ICU discharge. ICU and hospital length of stay was similar across all BMI classes. Adjusted ICU mortality was also similar when stratified by BMI. However, a significant reduction in post-ICU hospital mortality was observed in class I and II obese patients with cirrhosis (BMI 30-39.9 kg/m 2 ) compared to normal BMI (OR = 0.41; 95% CI, 0.20 to 0.83; P = 0.014). Similarly, overweight (BMI 25-29.9 kg/m 2 ) and class I and II obese patients with cirrhosis had significantly lower 30-day mortality following ICU discharge (OR = 0.52, 95% CI 0.31 to 0.87; P = 0.014; OR = 0.50, 95% CI 0.29 to 0.86; P = 0.012, respectively) compared to those with normal BMI. Conclusion: The signal of obesity paradox is suggested among critically ill patients with cirrhosis.

Background: Patients with sinus node dysfunction (SND) are at increased risk of atrial tachyarrhythmias, including atrial fibrillation (AF). Whether the presence of SND is also associated with worse outcomes among those with AF has not been well described. Methods: The ORBIT-AF registry enrolled patients with AF from a range of clinical practices across the US. SND was defined clinically, based on the presence of sinus bradycardia, severe sinus bradycardia, sinus arrest, sinoatrial exit block, or features of tachycardia-bradycardia syndrome. Descriptive statistics and multivariable logistic regression analysis were used to describe treatment patterns and outcomes for patients with and without SND and AF. Results: Overall, 1,710 (17.7%) patients had SND at enrollment. Patients with SND had lower left-ventricular ejection fractions, higher CHA 2 DS 2 -VASc risk scores, and more prior cerebrovascular events. Patients with SND had more severe symptoms (EHRA class IV: 17.5% vs. 13.9%; p=0.007) and poorer quality of life (median AFEQT 77.5 vs. 81.1; p=0.008) as compared to those without. SND patients were more frequently treated with oral anticoagulants (79.2% vs. 75.9%, p=0.004) and had more often received interventional therapy for AF (16.1% vs. 10.5%, p<0.0001). There were no differences in the current AF management strategy between patients with SND and those without [rate control (69.7% vs. 67.7%), rhythm control (30.0% vs. 32.0%); P=0.11]. After adjustment, significantly more patients with SND had progressed from paroxysmal AF at baseline to persistent or permanent AF at any follow-up or persistent AF at baseline to permanent AF at any follow-up than those without (OR 1.23, 95% CI 1.01-1.49, p=0.035). Conclusion: Sinus node dysfunction is associated worse symptoms, lower quality of life, and higher risk of progression to permanent AF. However, SND is not associated with increased risk of all-cause hospitalization, incident stroke, or all-cause death.

PURPOSE Many patients and physicians remain concerned about the potential detrimental effects of pregnancy after breast cancer (BC) in terms of reproductive outcomes and maternal safety. This systematic review and meta-analysis aimed at providing updated evidence on these topics. METHODS A systematic literature review was conducted to identify studies including patients with a pregnancy after BC (PROSPERO number CRD42020158324). Likelihood of pregnancy after BC, their reproductive outcomes, and maternal safety were assessed. Pooled relative risks, odds ratios (ORs), and hazard ratios (HRs) with 95% CIs were calculated using random effects models. RESULTS Of 6,462 identified records, 39 were included involving 8,093,401 women from the general population and 112,840 patients with BC of whom 7,505 had a pregnancy after diagnosis. BC survivors were significantly less likely to have a subsequent pregnancy compared with the general population (relative risk, 0.40; 95% CI, 0.32 to 0.49). Risks of caesarean section (OR, 1.14; 95% CI, 1.04 to 1.25), low birth weight (OR, 1.50; 95% CI, 1.31 to 1.73), preterm birth (OR, 1.45; 95% CI, 1.11 to 1.88), and small for gestational age (OR, 1.16; 95% CI, 1.01 to 1.33) were significantly higher in BC survivors, particularly in those with previous chemotherapy exposure, compared with the general population. No significantly increased risk of congenital abnormalities or other reproductive complications were observed. Compared to patients with BC without subsequent pregnancy, those with a pregnancy had better disease-free survival (HR, 0.66; 95% CI, 0.49 to 0.89) and overall survival (HR, 0.56; 95% CI, 0.45 to 0.68). Similar results were observed after correcting for potential confounders and irrespective of patient, tumor, and treatment characteristics, pregnancy outcome, and timing of pregnancy. CONCLUSION These results provide reassuring evidence on the safety of conceiving in BC survivors. Patients' pregnancy desire should be considered a crucial component of their survivorship care plan.

ABSTRACT Purpose: Evidence regarding the utility of systemic steroids in treating patients with cirrhosis and septic shock remains equivocal. This study aimed to evaluate and elucidate the association of steroid use with outcomes and adverse effects in a cohort of patients with cirrhosis and septic shock. Patients and methods: Retrospective cohort study of patients with cirrhosis and septic shock admitted to a tertiary hospital intensive care unit (ICU) from January 2007 to May 2017, using a validated ICU Datamart. Patients who received vasopressors within 6 h of ICU admission were included in the multivariate analysis. The effect of steroids on outcomes was evaluated using multivariable regression, adjusting for confounding variables. Results: Out of 179 admissions of patients with cirrhosis and septic shock, 56 received steroids during the ICU admission. Patients who received steroids received a higher total dose of vasopressors (91.2 mg vs. 39.1 mg, P = 0.04) and had a lower initial lactate level (1.8 mmol/L vs. 2.6 mmol/L, P = 0.007). The multivariate analysis included 117 patients and showed no significant differences in mortality, length of ICU admission, or length of hospital stay. Bleeding events, delirium, and renal-replacement therapy requirements were also not associated with the use of steroids. Conclusion: The use of systemic steroids was more prevalent in cirrhotic patients with higher vasopressor requirements. It was not associated with decreased mortality or increased ICU- and hospital-free days, or to adverse effects.