Citations

AbstractWe aimed to validate the prognostic association of p16 expression in ovarian high‐grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical‐grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis‐associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47–2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30–2.75, p = 0.004), while absence was associated with shorter OS in low‐grade serous carcinomas (HR: 2.95, 95% CI 1.61–5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype‐specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low‐grade serous carcinoma justifies CDK4 inhibition.

Objectives: Early results following arthroscopic superior capsular reconstruction(SCR) in patients with massive, irreparable rotator cuff tears are promising. However, no studies have compared patient reported outcomes between SCR or reverse total shoulder(rTSA) and rotator cuff debridement for these patients. Therefore, the purpose of this study was to compare 1-year outcomes between patients with massive irreparable rotator cuff tears who underwent a SCR, rTSA, or rotator cuff debridement with a concurrent biceps tenotomy or tenodesis. Methods: Patients(n=63) who underwent either SCR(n=21), rTSA(21), or cuff debridement(n=21) and biceps tenotomy or tenodesis for a massive, irreparable rotator cuff tear treated with a minimum 1-year follow up were retrospectively reviewed. Age, sex, BMI, smoking status, Charlson Index, Hamada classification, and ASES scores were recorded and compared using a multivariate ANOVA were used to compare between surgical approaches. A Chi Square analyses were used to compare sex distribution and the Charlson Deyo Index between groups (α=0.05). Results: Overall, patients across the 3 groups were not statistically different in age or follow up ASES score at minimum 14 month follow up ( P> 0.05). There was a significant interaction effect between surgery group and sex (P=0.02) on ASES score but not age ( P=0.08). Univariate F tests revealed that male patients who received an SCR displayed a 10-14% better outcome at follow up compared to other groups (Table 1) which exceeds the reported ASES score MCID. Conclusion: Our results show comparable results across surgical options for massive irreparable cuff tears with good patient reported outcomes. Male patients displayed clinically important greater ASES scores at 1 year follow up. Future studies should evaluate these preliminary results to assess if these preliminary results hold up at longer follow up times.

Over the past two decades, vitamin D level measurements have become some of the most frequently ordered tests in the laboratory. This increase is due to a growing awareness of widespread vitamin D deficiency and scientific data suggesting the beneficial effects of vitamin D in various diseases. A literature search was carried out in PubMed for cases reporting vitamin D intoxication and overdose. Thirteen articles were included in this review. Intoxication was severe in the reported cases. Patients presented with serum vitamin D concentrations ranging between 150 and 1220 ng/mL and serum calcium concentrations between 11.1 and 23.1 mg/dL. Most of the reported patients showed symptoms of vitamin D toxicity such as vomiting, dehydration, pain, and loss of appetite. The underlying causes included manufacturing errors, overdosing by patients or prescribers, and combinations of these factors. Our literature search highlights the fact that even though vitamin D intoxication is rare, it does occur and therefore patients and prescribers should be more cognizant of the potential dangers of vitamin D overdose.

Background: Controversy exists as to whether the subscapularis should be repaired after reverse shoulder arthroplasty. The purpose of the present study was to evaluate the utility of repairing the subscapularis after reverse shoulder arthroplasty with regard to complications, objective findings, and patient-reported outcome measures. Methods: We retrospectively reviewed the records for 99 patients who had undergone a lateralized reverse shoulder arthroplasty with (n = 58) or without (n = 41) subscapularis repair. Outcomes were compared with the Single Assessment Numeric Evaluation (SANE), Penn shoulder score (PSS), Veterans RAND (VR)-12, and American Shoulder and Elbow Surgeons (ASES) score at a minimum of 2 years of follow-up. Demographics, range of motion, and complications were also compared. A 1-way analysis of variance was performed to determine differences in performance and outcome scores, and a chi-square analysis was performed to compare the frequency of complications between groups. Results: There were no significant differences between the repair and no-repair groups in terms of SANE, PSS, ASES, or VR-12 scores. There also were no significant differences between the 2 groups in terms of postoperative ranges of forward elevation (128° versus 123°; p = 0.44) and external rotation (33° versus 29°; p = 0.29), the dislocation rate (5% versus 2%; p = 0.49), or the overall complication rate (9% versus 5%; p = 0.47). Conclusions: The results of the present study suggest that repair of the subscapularis tendon after lateralized reverse shoulder arthroplasty may not be necessary. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Background: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. Methods and Results: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464–1610), and structural heart disease. Conclusions: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01920711.

Objectives Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early‐onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD‐ and schizophrenia (SCZ)‐associated risk variants is associated with an earlier AAO in BD patients. Methods A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn‐Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD‐ and SCZ‐PRSs and AAO were evaluated with regression models. Results BD‐ and SCZ‐PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment. Conclusions The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.