18F-fluoro-ethyl-tyrosine PET co-registered with MRI in patients with persisting acromegaly.

OBJECTIVE: To report our experience with 18F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRICR) in the care trajectory for persistent acromegaly. DESIGN: Prospective case series. PATIENTS: Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options. MEASUREMENTS: FET-PET/MRICR was used to support decision-making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery. RESULTS: FET-PET/MRICR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET-PET/MRICR was fully concordant with conventional MRI, and in one patient partially concordant. FET-PET/MRICR identified suggestive new foci in four other patients. Surgical re-exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET-PET/MRICR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF-1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients. CONCLUSIONS: In patients with persisting acromegaly without a clear surgical target on MRI, FET-PET/MRICR is a new tracer to provide additional information to aid decision-making by the multidisciplinary pituitary team.

Periodontitis: A Plausible Modifiable Risk Factor for Neurodegenerative Diseases? A Comprehensive Review.

The aim of this comprehensive review is to summarize recent literature on associations between periodontitis and neurodegenerative diseases, explore the bidirectionality and provide insights into the plausible pathogenesis. For this purpose, systematic reviews and meta-analyses from PubMed, Medline and EMBASE were considered. Out of 33 retrieved papers, 6 articles complying with the inclusion criteria were selected and discussed. Additional relevant papers for bidirectionality and pathogenesis were included. Results show an association between periodontitis and Alzheimer's disease, with odds ratios of 3 to 5. A bidirectional relationship is suspected. For Parkinson's disease (PD), current evidence for an association appears to be weak, although poor oral health and PD seem to be correlated. A huge knowledge gap was identified. The plausible mechanistic link for the association between periodontitis and neurodegenerative diseases is the interplay between periodontal inflammation and neuroinflammation. Three pathways are hypothesized in the literature, i.e., humoral, neuronal and cellular, with a clear role of periodontal pathogens, such as Porphyromonas gingivalis. Age, gender, race, smoking, alcohol intake, nutrition, physical activity, socioeconomic status, stress, medical comorbidities and genetics were identified as common risk factors for periodontitis and neurodegenerative diseases. Future research with main emphasis on the collaboration between neurologists and dentists is encouraged.

Online prediction tools for melanoma survival: A comparison.

BACKGROUND: Breslow thickness, patient age and ulceration are the three most valuable clinical and pathological predictors of melanoma survival. A readily available reliable online tool that accurately considers these and other predictors could be valuable for clinicians managing melanoma patients. OBJECTIVE: To compare online melanoma survival prediction tools that request user input on clinical and pathological features. METHODS: Search engines were used to identify available predictive nomograms. For each, clinical and pathological predictors were compared. RESULTS: Three tools were identified. The American Joint Committee on Cancer tool inappropriately rated thin tumours as higher risk than intermediate tumours. The University of Louisville tool was found to have six shortcomings: a requirement for sentinel node biopsy, unavailable input of thin melanoma or patients over 70 years of age and less reliable hazard ratio calculations for age, ulceration and tumour thickness. The LifeMath.net tool was found to appropriately consider tumour thickness, ulceration, age, sex, site and tumour subtype in predicting survival. LIMITATIONS: The authors did not have access to the base data used to compile various prediction tools. CONCLUSION: The LifeMath.net prediction tool is the most reliable for clinicians in counselling patients with newly diagnosed primary cutaneous melanoma regarding their survival prospects.

Enhanced HPV16 E6/E7+ tumor eradication via induction of tumor-specific T cells by therapeutic vaccination with virosomes presenting synthetic long peptides.

Therapeutic cancer vaccines trigger CD4 + and CD8 + T cell responses capable of established tumor eradication. Current platforms include DNA, mRNA and synthetic long peptide (SLP) vaccines, all aiming at robust T cell responses. SLPs linked to the Amplivant® adjuvant (Amplivant-SLP) have shown effective delivery to dendritic cells, resulting in improved immunogenicity in mice. We have now tested virosomes as a delivery vehicle for SLPs. Virosomes are nanoparticles made from influenza virus membranes and have been used as vaccines for a variety of antigens. Amplivant-SLP virosomes induced the expansion of more antigen-specific CD8 + T memory cells in ex vivo experiments with human PBMCs than Amplivant-SLP conjugates alone. The immune response could be further improved by including the adjuvants QS-21 and 3D-PHAD in the virosomal membrane. In these experiments, the SLPs were anchored in the membrane through the hydrophobic Amplivant adjuvant. In a therapeutic mouse model of HPV16 E6/E7+ cancer, mice were vaccinated with virosomes loaded with either Amplivant-conjugated SLPs or lipid-coupled SLPs. Vaccination with both types of virosomes significantly improved the control of tumor outgrowth, leading to elimination of the tumors in about half the animals for the best combinations of adjuvants and to their survival beyond 100 days.

Implications of disparate uterine and ovarian development observed among heifers evaluated during the peripubertal period.

The incidence and implications of disparate ovarian and uterine development during the peripubertal period were evaluated in two experiments. In Experiment 1, two consecutive pre-breeding evaluations were performed on 469 heifers. In Experiment 2, data from 22,174 heifers were retrospectively analyzed. For heifers in both experiments, ovarian and uterine maturity were independently assessed via transrectal evaluation, and a two-digit reproductive tract score (RTS: first digit = ovarian; second digit = uterine) was assigned. Measures of the physical maturity of heifers were recorded at the time of pre-breeding evaluation. Heifers were subjected to 14-day progestin-based protocols for synchronization of estrus, and artificial insemination (AI) was performed. Pregnancy diagnosis was performed via transrectal ultrasonography. Incidence of disparate ovarian and uterine score was 33.7 % (158/469) in Experiment 1 % and 16.3 % (3622/22,174) in Experiment 2. Observations of disparate ovarian and uterine maturity were correlated with physical maturity. Heifers with RTS < 3-3 demonstrated poor reproductive performance, as lesser proportions of these animals conceived to the first AI service in Experiment 2 (P < 0.01) or throughout the breeding season in Experiment 1 (P = 0.03). Conception did not differ between heifers assigned congruent or disparate scores of greater than RTS = 3-3. Disparities in ovarian and uterine development are likely observed as the result of rapid, yet asynchronous growth of reproductive tissues during the peripubertal period and are not indicative of inherently reduced potential for fertility. Independent assessment of ovarian and uterine maturity may increase precision in characterizing physiologic maturity of mixed groups of prepubertal, peripubertal, and pubertal heifers.

Common Reference-Based Tandem Mass Tag Multiplexing for the Relative Quantification of Peptides: Design and Application to Degradome Analysis of Diphtheria Toxoid.

Currently, animal tests are being used to confirm the potency and lack of toxicity of toxoid vaccines. In a consistency approach, animal tests could be replaced if production consistency (compared to known good products) can be proven in a panel of in vitro assays. By mimicking the in vivo antigen processing in a simplified in vitro approach, it may be possible to distinguish aberrant products from good products. To demonstrate this, heat-exposed diphtheria toxoid was subjected to partial digestion by cathepsin S (an endoprotease involved in antigen processing), and the peptide formation/degradation kinetics were mapped for various heated toxoids. To overcome the limitations associated with the very large number of samples, we used common reference-based tandem mass tag (TMT) labeling. Instead of using one label per condition with direct comparison between the set of labels, we compared multiple labeled samples to a common reference (a pooled sample containing an aliquot of each condition). In this method, the number of samples is not limited by the number of unique TMT labels. This TMT multiplexing strategy allows for a 15-fold reduction of analysis time while retaining the reliability advantage of TMT labeling over label-free quantification. The formation of the most important peptides could be followed over time and compared among several conditions. The changes in enzymatic degradation kinetics of diphtheria toxoid revealed several suitable candidate peptides for use in a quality control assay that can distinguish structurally aberrant diphtheria toxoid from compliant toxoids.

Complications and survival after hybrid and fully minimally invasive oesophagectomy.

BACKGROUND: Minimally invasive oesophagectomy (MIO) is reported to produce fewer respiratory complications than open oesophagectomy. This study assessed differences in postoperative complications between MIO and hybrid MIO (HMIO) employing thoracoscopy and laparotomy, along with the influence of co-morbidities on postoperative outcomes. METHODS: Patients with oesophageal cancer undergoing three-stage MIO or three-stage HMIO between 1999 and 2018 were identified from a prospectively developed database, which included patient demographics, co-morbidities, preoperative therapies, and cancer stage. The primary outcome was postoperative complications in the two groups. Secondary outcomes included duration of operation, blood transfusion requirement, duration of hospital stay, and overall survival. RESULTS: There were 828 patients, of whom 722 had HMIO and 106 MIO, without significant baseline differences. Median duration of operation was longer for MIO (325 versus 289 min; P < 0.001), but with less blood loss (median 250 versus 300 ml; P < 0.001) and a shorter hospital stay (median 12 versus 13 days; P = 0.006). Respiratory complications were not associated with operative approach (31.1 versus 35.2 per cent for MIO and HMIO respectively; P = 0.426). Anastomotic leak rates (10.4 versus 10.2 per cent) and 90-day mortality (1.0 versus 1.7 per cent) did not differ. Cardiac co-morbidity was associated with more medical and surgical complications. Overall survival was associated with AJCC stage and co-morbidities, but not operative approach. CONCLUSION: MIO had a small benefit in terms of blood loss and hospital stay, but not in operating time. Oncological outcomes were similar in the two groups. Postoperative complications were associated with pre-existing cardiorespiratory co-morbidities rather than operative approach.

Evaluation of later timepoints for split-time artificial insemination when using sex-sorted semen among beef heifers following the 14-d CIDR®-PG protocol.

An experiment was designed to evaluate later timepoints for Split-Time AI (STAI), with the hypothesis that delaying AI may improve estrous response and pregnancy per AI when using sex-sorted semen. Timing of estrus was synchronized among 794 heifers using the 14-d CIDR®-PG protocol (1.38 g progesterone intravaginal insert from Day 0-14, followed by 25 mg dinoprost tromethamine on Day 30) with STAI performed based on estrous status. Heifers were blocked based on breed, source, sire, reproductive tract score (RTS), and BW and assigned within block to one of two approaches. In Approach 66, heifers that were estrual by 66 h after PG administration were inseminated at 66 h, and remaining heifers were inseminated 24 h later (90 h). In Approach 72, heifers that were estrual by 72 h were inseminated at 72 h, and remaining heifers were inseminated 24 h later (96 h). With both approaches, heifers that were non-estrual by the final timepoint were administered 100 µg gonadorelin acetate (GnRH). Within approach, heifers were pre-assigned to receive SexedULTRA 4M™ sex-sorted or conventional semen. The proportion of heifers estrual by the first timepoint was greater (P < 0.0001) with Approach 72 (76 %; 302/395) compared to Approach 66 (61 %; 242/399). The proportion of heifers pregnant as a result of AI differed (P = 0.0005) by semen type (59 % [240/404] for conventional compared with 48 % [187/390] for sex-sorted) but was not affected by approach or approach × semen type. In summary, pregnancy per AI of heifers receiving sex-sorted or conventional semen following the 14-d CIDR®-PG protocol did not differ when STAI was delayed 6 h. The proportion of estrual heifers prior to the first timepoint, however, was greater with later STAI.

Delayed Extension Block Pinning in 27 Patients With Mallet Fracture.

Background: Untreated bony mallet fingers can cause an array of problems; therefore, adequate treatment is essential. The primary aim of this study was to determine the patient-reported functional outcome of delayed surgical intervention of bony mallet fingers. The secondary aim was to determine the complication rate of delayed surgical intervention. Methods: In this single-center retrospective cohort study, all consecutive patients treated between 2010 and 2016 at our level 2 regional teaching hospital were included. Inclusion criterion was a bony mallet finger injury (excluding the thumb), presenting >21 days after injury, treated with extension block pinning. Indications for surgery were >2 mm fragment displacement or volar subluxation of the distal interphalangeal joint. Six to 82 months postoperatively, patients completed the Patient-Rated Wrist and Hand Evaluation (PRWHE) by phone. Complications were extracted by chart review. Results: Twenty-seven patients were included, and all completed the PRWHE. Median time to surgery was 35 days (interquartile range [IQR] = 29-42; range = 22-61). Reasons for delay in surgical treatment were patient/physician delay in 24 cases and failed conservative treatment in 3 cases. The median PRWHE score was 0 (IQR = 0-5; range = 0-22.5). After retrospective assessment of the outpatient charts, no early symptoms of malunion or nonunion were found. One patient had a loss of Kirschner-wire fixation, which was corrected. Three patients had an infection that required antibiotic treatment. Conclusions: Delayed surgical management of bony mallet fingers demonstrated adequate functional outcome with minimal complications when compared with prior literature.

Comparison of the 7 & 7 Synch protocol and the 7-day CO-Synch + CIDR protocol among recipient beef cows in an embryo transfer program.

An experiment was designed to evaluate the effectiveness of the recently developed 7 & 7 Synch protocol to synchronize estrus among recipients prior to embryo transfer (ET). Postpartum beef cows (n = 1358) across thirteen locations were assigned to either the 7-d CO-Synch + CIDR protocol or the 7 & 7 Synch protocol prior to ET. Cows were preassigned to balanced treatments within location based on age and days postpartum, with body condition score recorded at ET. Cows assigned to the 7-d CO-Synch + CIDR protocol were administered gonadotropin-releasing hormone (GnRH; 100 µg gonadorelin acetate) on Day 7, an intravaginal controlled internal drug release (CIDR; 1.38 g progesterone) from Day 7 to Day 14, and prostaglandin F2α (PGF2α; 25 mg dinoprost tromethamine) coincident with CIDR removal on Day 14. Cows assigned to the 7 & 7 Synch protocol were administered PGF2α (25 mg dinoprost tromethamine) coincident with CIDR insertion on Day 0, GnRH (100 µg gonadorelin acetate) on Day 7, and PGF2α (25 mg dinoprost tromethamine) coincident with CIDR removal on Day 14. Cows were observed for visible signs of estrus, with GnRH (100 µg gonadorelin acetate) administered to cows failing to express estrus during the detection period. Embryo transfer was performed approximately seven days after estrus or GnRH administration. Presence of corpora lutea (CL) was determined via transrectal palpation by a single veterinarian blinded to treatment, and embryos were transferred only to cows with palpable CL. Embryo transfer was performed using either fresh or frozen embryos, with embryo stage and grade recorded for each recipient. The proportion of cows expressing estrus was increased (P < 0.0001) among cows assigned to the 7 & 7 Synch protocol (86% [529/615] vs 76% [488/640]). The proportion of cows expressing estrus and presenting with palpable CL at ET was greater (P < 0.0001) among cows following treatment with the 7 & 7 Synch protocol compared to the 7-d CO-Synch + CIDR protocol (76% [466/615] vs 65% [418/640]). Consequently, the proportion pregnant to ET was greater (P < 0.03) following the 7 & 7 Synch protocol (40% [263/653]) compared to the 7-d CO-Synch + CIDR protocol (34% [228/664]). In summary, the 7 & 7 Synch protocol involving administration of PGF2α and treatment with a CIDR for 7 days prior to GnRH improved the likelihood of estrus expression in recipients, increased the proportion of cows eligible to receive an embryo, which resulted in a greater pregnancy rate to ET.

Novel Formaldehyde-Induced Modifications of Lysine Residue Pairs in Peptides and Proteins: Identification and Relevance to Vaccine Development.

Formaldehyde-inactivated toxoid vaccines have been in use for almost a century. Despite formaldehyde's deceptively simple structure, its reactions with proteins are complex. Treatment of immunogenic proteins with aqueous formaldehyde results in heterogenous mixtures due to a variety of adducts and cross-links. In this study, we aimed to further elucidate the reaction products of formaldehyde reaction with proteins and report unique modifications in formaldehyde-treated cytochrome c and corresponding synthetic peptides. Synthetic peptides (Ac-GDVEKGAK and Ac-GDVEKGKK) were treated with isotopically labeled formaldehyde (13CH2O or CD2O) followed by purification of the two main reaction products. This allowed for their structural elucidation by (2D)-nuclear magnetic resonance and nanoscale liquid chromatography-coupled mass spectrometry analysis. We observed modifications resulting from (i) formaldehyde-induced deamination and formation of α,ß-unsaturated aldehydes and methylation on two adjacent lysine residues and (ii) formaldehyde-induced methylation and formylation of two adjacent lysine residues. These products react further to form intramolecular cross-links between the two lysine residues. At higher peptide concentrations, these two main reaction products were also found to subsequently cross-link to lysine residues in other peptides, forming dimers and trimers. The accurate identification and quantification of formaldehyde-induced modifications improves our knowledge of formaldehyde-inactivated vaccine products, potentially aiding the development and registration of new vaccines.

Treatment with prostaglandin F2α and an intravaginal progesterone insert promotes follicular maturity in advance of gonadotropin-releasing hormone among postpartum beef cows.

An experiment was designed to evaluate treatments to promote ovarian follicular maturity in advance of administration of exogenous gonadotropin-releasing hormone (GnRH; 100 µg gonadorelin) for control of the bovine estrous cycle. We hypothesized prostaglandin F2α (PGF2α; 500 µg cloprostenol) followed by an intravaginal progesterone-releasing insert (CIDR; 1.38 g progesterone) would induce greater follicle size and serum estradiol at the time of GnRH administration. Postpartum cows (n = 194) in two locations were assigned to one of five treatments based on age, days postpartum, and body condition score. Cows in Treatment 1 were treated with the standard 7-d CO-Synch + CIDR protocol: administration of GnRH and CIDR insertion on Day -10, and administration of PGF2α and CIDR removal on Day -3. Treatments 2-5 were designed in a 2 × 2 factorial arrangement, with Treatment 1 included as an additional reference. On Day -17, cows in Treatments 2-5 received a CIDR insert, either with (Treatments 2 and 3) or without (Treatments 4 and 5) administration of PGF2α at CIDR insertion. On Day -10, all cows were administered GnRH, and CIDR inserts were either removed (Treatments 2 and 4) or remained in place until Day -3 (Treatments 3 and 5). Treatment with PGF2α and CIDR in advance of GnRH (Treatments 2 and 3) resulted in increased diameter of the largest ovarian follicle (P < 0.001) and increased serum concentrations of estradiol (P < 0.0005) on Day -10. In addition, variation among cows in CL status (no CL vs. a single CL vs. multiple CL) on Day -3 tended to be decreased (P = 0.08), with cows more likely to have a single CL rather than no CL or multiple CL. Lastly, the proportion of cows expressing estrus prior to fixed-time artificial insemination tended (P = 0.08) to be improved. Results support the hypothesis that administration of PGF2α and treatment with a CIDR for 7 days prior to GnRH promotes follicular maturity in advance of GnRH administration and may provide an approach by which to enhance response of postpartum beef cows to GnRH-based estrus synchronization programs.

Formaldehyde treatment of proteins enhances proteolytic degradation by the endo-lysosomal protease cathepsin S.

Enzymatic degradation of protein antigens by endo-lysosomal proteases in antigen-presenting cells is crucial for achieving cellular immunity. Structural changes caused by vaccine production process steps, such as formaldehyde inactivation, could affect the sensitivity of the antigen to lysosomal proteases. The aim of this study was to assess the effect of the formaldehyde detoxification process on the enzymatic proteolysis of antigens by studying model proteins. Bovine serum albumin, ß-lactoglobulin A and cytochrome c were treated with various concentrations of isotopically labelled formaldehyde and glycine, and subjected to proteolytic digestion by cathepsin S, an important endo-lysosomal endoprotease. Degradation products were analysed by mass spectrometry and size exclusion chromatography. The most abundant modification sites were identified by their characteristic MS doublets. Unexpectedly, all studied proteins showed faster proteolytic degradation upon treatment with higher formaldehyde concentrations. This effect was observed both in the absence and presence of glycine, an often-used excipient during inactivation to prevent intermolecular crosslinking. Overall, subjecting proteins to formaldehyde or formaldehyde/glycine treatment results in changes in proteolysis rates, leading to an enhanced degradation speed. This accelerated degradation could have consequences for the immunogenicity and the efficacy of vaccine products containing formaldehyde-inactivated antigens.

Manno-epi-cyclophellitols Enable Activity-Based Protein Profiling of Human α-Mannosidases and Discovery of New Golgi Mannosidase II Inhibitors.

Golgi mannosidase II (GMII) catalyzes the sequential hydrolysis of two mannosyl residues from GlcNAcMan5GlcNAc2 to produce GlcNAcMan3GlcNAc2, the precursor for all complex N-glycans, including the branched N-glycans associated with cancer. Inhibitors of GMII are potential cancer therapeutics, but their usefulness is limited by off-target effects, which produce α-mannosidosis-like symptoms. Despite many structural and mechanistic studies of GMII, we still lack a potent and selective inhibitor of this enzyme. Here, we synthesized manno-epi-cyclophellitol epoxide and aziridines and demonstrate their covalent modification and time-dependent inhibition of GMII. Application of fluorescent manno-epi-cyclophellitol aziridine derivatives enabled activity-based protein profiling of α-mannosidases from both human cell lysate and mouse tissue extracts. Synthesized probes also facilitated a fluorescence polarization-based screen for dGMII inhibitors. We identified seven previously unknown inhibitors of GMII from a library of over 350 iminosugars and investigated their binding modalities through X-ray crystallography. Our results reveal previously unobserved inhibitor binding modes and promising scaffolds for the generation of selective GMII inhibitors.

Comparison of long-term progestin-based protocols to synchronize estrus prior to natural service or fixed-time artificial insemination in Bos indicus-influenced beef heifers.

This experiment was designed to evaluate breeding strategies involving natural service or fixed-time artificial insemination (FTAI) in Bos indicus-influenced beef heifers (n = 1456) when there were field-type management conditions. Body weights and reproductive tract scores (RTS; Scale 1-5) were obtained for heifers before assignment to one of five treatments: 1) Non-synchronized control exposed for natural service (NS), n = 299; 2) melengestrol acetate + natural service (MGA + NS; 0.5 mg/heifer/d), n = 295; 3) 14-d controlled internal drug release insert + natural service (CIDR + NS), n = 289; 4) 14-d MGA-prostaglandin F2α (PG) + FTAI, n = 295; or 5) 14-d CIDR-PG + FTAI, n = 278. Fertile bulls were placed in pastures with heifers of the three NS treatment groups for a 65-day period which began 10 days after progestin treatments (MGA or CIDR) ended. Heifers in FTAI treatment groups were administered PG (25 mg, IM) 16 days after CIDR removal or 19 days following MGA withdrawal, respectively, and FTAI was performed at 66 (CIDR-PG) or 72 h (MGA-PG) after PG. Gonadotropin-releasing hormone (GnRH; 100 µg, i.m.) was administered at FTAI. Pregnancy status was determined at the end of a 65-day breeding period. Pregnancy rates on Days 21 and 65 of the breeding period differed among treatment groups based on pre-treatment pubertal status (P ≤ 0.02) and body weight (P ≤ 0.05) but did not differ by group. These data highlight the need for continued research efforts to improve reproductive management of Bos indicus-influenced females.

Baseline neutrophil-lymphocyte ratio holds no prognostic value for esophageal and junctional adenocarcinoma in patients treated with neoadjuvant chemotherapy.

BACKGROUND: Several studies have reported that neutrophil-lymphocyte ratio (NLR) can predict survival in esophageal and gastroesophageal junction adenocarcinoma, as it reflects systemic inflammation. Hence, we aimed to determine whether baseline NLR holds prognostic value for esophageal adenocarcinoma patients treated with neoadjuvant chemotherapy (nCT) followed by surgery. METHODS: We studied the data of 139 patients that received nCT before undergoing esophagectomy with curative intent, all identified from a prospectively maintained database (1998-2016). Pretreatment hematology reports were used to calculate the baseline NLR. A receiver operating characteristic curve (ROC-curve) was plotted to determine an optimal cutoff value. NLR quartiles were used to display possible differences between groups in relation to overall survival (OS) and disease-free survival (DFS) using the method of Kaplan-Meier. Cox regression analysis was performed to assess the prognostic value of NLR. RESULTS: The median OS and DFS times were 46 months (interquartile range [IQR]: 19-166) and 30 months (IQR: 13-166], respectively, for the entire cohort. The ROC-curve showed that NLR has no discriminating power for survival status (area under the curve = 0.462) and therefore no optimal cutoff value could be determined. There were no statistically significant differences in median OS times for NLR quartiles: 65 (Q1), 32 (Q2), 45 (Q3), and 46 months (Q4) (P = 0.926). Similarly, DFS showed no difference between quartile groups, with median survival times of 27 (Q1), 19 (Q2), 36 (Q3), and 20 months (Q4) (P = 0.973). Age, pN, pM, and resection margin were independent prognostic factors for both OS and DFS. On the contrary, NLR was not associated with OS or DFS in univariable and multivariable analyses. CONCLUSION: Baseline NLR holds no prognostic value for esophageal and gastroesophageal junction adenocarcinoma patients treated with nCT in this study, in contrast to other recently published papers. This result questions the validity of NLR as a reliable prognostic indicator and its clinical usefulness in these patients.

Patient-Reported Outcomes and Complications After Surgical Fixation of 143 Proximal Phalanx Fractures.

PURPOSE: Multiple methods exist to surgically fix unstable phalangeal fractures. Whereas these methods have different rates of complications or reoperation, it is not known whether these differences lead to changes in patient reported outcome. We compared patient-reported outcomes measures and complications of Kirschner wire (K-wire), lag-screw and plate fixation of proximal phalanx fractures (excluding the thumb). METHODS: From 2010 to 2015, 159 patients with 159 proximal phalanx fractures were identified in 2 level 2 trauma centers and fixed with K-wires (44% of patients), lag-screws (26%), or plates (30%). Disabilities of the Arm, Shoulder, and Hand (DASH), and Patient-Rated Wrist/Hand Evaluation (PRWHE) and complications were assessed. In addition, subjective outcomes were assessed. Follow-up was achieved for 143 fractures (90%) and average time to follow-up was 3.4 years. RESULTS: Mean DASH and PRWHE scores were 5.0 and 8.2, respectively. No differences in functional outcomes were found between fixation methods, although unplanned reoperation was more common in the plate fixation group (9 patients; 21%) than in the K-wire and lag-screw fixation groups (3 patients and 1 patient; 4.8 and 2.7%, respectively). We also found that K-wire fixation was associated with better aesthetic outcome than open reduction internal fixation. CONCLUSIONS: Overall patient-reported outcomes measure scores were similar across fixation methods, and unplanned reoperation was more prevalent after plate fixation. In addition, we found that regardless of fracture pattern, percutaneous fixation with K-wires was often sufficient and associated with better aesthetic outcome than open reduction and internal fixation. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Altering duration of the presynchronization period in a long-term progestin-based estrus synchronization protocol for timed artificial insemination of beef heifers.

An experiment was designed to evaluate the effect of extending duration of the presynchronization treatment in a long-term progestin-based estrus synchronization protocol. Heifers were assigned to either an 18 d (Day 0-18) or 14 d (Day 4 to Day 18) CIDR® treatment (1.38 g progesterone controlled internal drug release insert; Zoetis, Madison, NJ), with prostaglandin F2α (PG; 250 µg im cloprostenol sodium) administered 16 d after CIDR® removal (Day 34). Heifers at two locations (location one, n = 193; location two, n = 649) were assigned to treatment based on reproductive tract score (RTS; Scale 1-5) and body weight. Heifers that were assigned RTS 1 were not retained for the trial (n = 6). Estrus detection aids (Estrotect®) were applied at PG. Split-time artificial insemination (STAI) was utilized and AI performed based on expression of estrus at 66 h. Expression of estrus was defined as removal of ≥50% of the grey coating from the Estrotect® patch. Heifers that expressed estrus at 66 h were inseminated then and heifers that had not expressed estrus were inseminated at 90 h. Only heifers that failed to express estrus by 90 h received gonadotropin-releasing hormone (GnRH; 100 µg im gonadorelin acetate) at the time of AI. At location one, blood samples were collected at PG and AI (66 h or 90 h) from all heifers to determine E2 concentration by radioimmunoassay, and transrectal ovarian ultrasound was performed to detail ovarian structures on a subset of heifers (n = 73) at both time points. The proportion of heifers expressing estrus did not differ between treatments, either by 66 h (60%) or in total by 90 h (84%) after PG. Pregnancy rate to STAI did not differ between treatments (P = 0.3; 52%, 14-d CIDR®-PG; 50%, 18-d CIDR®-PG), or at the end of the 60 d breeding season (P = 0.2; 86%, 14-d CIDR®-PG; 82%, 18-d CIDR®-PG). No differences were detected in mean diameter of the dominant follicle at PG (P = 0.6; 10.9 ±â€¯0.4 mm, 14-d CIDR®-PG; 11.0 ±â€¯0.4 mm, 18-d CIDR®-PG) or at STAI (P = 0.3; 12.6 ±â€¯0.4 mm, 14-d CIDR®-PG; 13.2 ±â€¯0.4 mm, 18-d CIDR®-PG), nor were any differences observed between treatments in concentrations of E2 at PG (P = 0.8; 1.1 ±â€¯0.19 pg/ml, 14-d CIDR®-PG; 1.1 ±â€¯0.19 pg/ml, 18-d CIDR®-PG) or STAI (P = 0.6; 3.8 ±â€¯0.19 pg/ml, 14-d CIDR®-PG; 3.6 ±â€¯0.19 pg/ml, 18-d CIDR®-PG). These data indicate that duration of CIDR® treatment can be extended from 14 to 18 d, thus providing flexibility in scheduling without compromising reproductive outcomes.