The location of the peroneus longus tendon in the cuboid groove: sonographic study in various positions of the ankle–foot in asymptomatic volunteers

Abstract

Objective

To evaluate the normal location of the peroneus longus tendon (PL) in the cuboid groove in various ankle–foot positions by ultrasonography in asymptomatic volunteers.

Materials and methods

Ultrasonographic assessment of the PL in the cuboid groove was performed in 20 feet of ten healthy volunteers. Each PL was examined in five ankle–foot positions (i.e., neutral, dorsiflexion, plantar-flexion, supination, and pronation). The PL location was qualitatively categorized as "inside" when the PL was entirely within the cuboid groove, as "overlying" when some part of the PL was perched on the cuboid tuberosity, and as "outside" when the PL was entirely on the cuboid tuberosity. For quantitative evaluation of the PL location, the distance between the PL and the cuboid groove was measured. The width of the cuboid groove was measured in the neutral position.

Results

The PL location did not significantly change with changes in the ankle–foot position. Qualitatively, an "overlying" PL was the most common type, regardless of the ankle–foot position. "Inside" PLs were found in only 35, 20, 30, 25, and 35% of feet in neutral, dorsiflexion, plantar-flexion, supination, and pronation positions, respectively. The quantitative PL location was also not significantly different among all ankle–foot positions and it was significantly negatively correlated with the cuboid groove width.

Conclusions

In healthy volunteers, 65% or more of the PLs were partially or completely located outside of the cuboid groove, regardless of the ankle–foot position. The PL location relative to the cuboid groove was related to the cuboid groove width.

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Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined 18 F-FDG and 18 F-FLT PET/CT imaging

Abstract

Background

Despite the significant upgrading in recent years of the role of ¹⁸F-FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for myeloma-specific radiotracers. 3′-Deoxy-3′-[¹⁸F]fluorothymidine (¹⁸F-FLT) is the most studied cellular proliferation PET agent, considered a potentially new myeloma functional imaging tracer. The aim of this pilot study was to evaluate ¹⁸F-FLT PET/CT in imaging of MM patients, in the context of its combined use with ¹⁸F-FDG PET/CT.

Results

Eight patients, four suffering from symptomatic MM and four suffering from smoldering MM (SMM), were enrolled in the study. All patients underwent ¹⁸F-FDG PET/CT and ¹⁸F-FLT PET/CT imaging by means of static (whole body) and dynamic PET/CT of the lower abdomen and pelvis (dPET/CT) in two consecutive days. The evaluation of PET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modeling. ¹⁸F-FDG PET/CT demonstrated focal, ¹⁸F-FDG avid, MM-indicative bone marrow lesions in five patients. In contrary, ¹⁸F-FLT PET/CT showed focal, ¹⁸F-FLT avid, myeloma-indicative lesions in only two patients. In total, 48 ¹⁸F-FDG avid, focal, MM-indicative lesions were detected with ¹⁸F-FDG PET/CT, while 17 ¹⁸F-FLT avid, focal, MM-indicative lesions were detected with ¹⁸F-FLT PET/CT. The number of myeloma-indicative lesions was significantly higher for ¹⁸F-FDG PET/CT than for ¹⁸F-FLT PET/CT. A common finding was a mismatch of focally increased ¹⁸F-FDG uptake and reduced ¹⁸F-FLT uptake (lower than the surrounding bone marrow). Moreover, ¹⁸F-FLT PET/CT was characterized by high background activity in the bone marrow compartment, further complicating the evaluation of bone marrow lesions. Semi-quantitative evaluation revealed that both SUV_mean and SUV_max were significantly higher for ¹⁸F-FLT than for ¹⁸F-FDG in both MM lesions and reference tissue. SUV values were higher in MM lesions than in reference bone marrow for both tracers.

Conclusions

Despite the limited number of patients analyzed in this pilot study, the first results of the trial indicate that ¹⁸F-FLT does not seem suitable as a single tracer in MM diagnostics. Further studies with a larger patient population are warranted to generalize the herein presented results.

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Why does chemotherapy stop affecting the cells of ovarian and breast tumors?

Future Oncology, Ahead of Print.


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The effect of Glut1 and c-myc on prognosis in esophageal squamous cell carcinoma of Kazakh and Han patients

Future Oncology, Ahead of Print.


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Use of lymphoscintigraphy to differentiate primary versus secondary lower extremity lymphedema after surgical lymphadenectomy: a retrospective analysis

Abstract

Background

When managing patients with cancer, lymphedema of the lower limbs (LLL) is commonly reported as secondary to the surgical excision and/or irradiation of lymph nodes (LNs). In the framework of lymphoscintigraphic imaging performed to evaluate secondary LLL, some lympho-nodal presentations have been observed that could not be explained by the applied treatments, suggesting that these LLL might be primary. Therefore, all our lymphoscintigraphic examinations that were performed in patients for LLL after surgery for gynecological or urological cancer were retrospectively analyzed in order to evaluate the frequency in which these LLL might not be secondary (either completely or partially) but primary in origin.

Methods

Lymphoscintigraphies performed in 33 patients who underwent LN dissection (limited to the intra-abdominal LN) with or without radiotherapy for histologically confirmed ovarian cancer (n = 6), uterine cancer (n = 14 with cervical cancer and n = 7 with endometrial cancer), or prostate cancer (n = 6) were compared to lymphoscintigraphies obtained in primary LLL.

Results

In 12 (33% of the) patients (3 men plus 9 women, 4 with cervical cancer and 5 with endometrial cancer), scintigraphy of the lower limbs revealed lympho-nodal presentation that did not match with the expected consequences of the surgical and/or radiological treatments and were either suggestive or typical of primary lymphedema.

Conclusions

This retrospective analysis of a limited but well-defined series of patients suggests that the appearance of LLL might not be related to cancer treatment(s) but that these LLL may represent the development of a primary lymphatic disease latent prior to the therapeutic interventions.

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Sex Differences in Recombination in Sticklebacks

Recombination often differs markedly between males and females. Here we present the first analysis of sex-specific recombination in Gasterosteus sticklebacks. Using whole-genome sequencing of 15 crosses between G. aculeatus and G. nipponicus, we localized 698 crossovers with a median resolution of 2.3 kb. We also used a bioinformatic approach to infer historical sex-averaged recombination patterns for both species. Recombination is greater in females than males on all chromosomes, and overall map length is 1.64 times longer in females. The locations of crossovers differ strikingly between sexes. Crossovers cluster towards chromosome ends in males, but are distributed more evenly across chromosomes in females. Suppression of recombination near the centromeres in males causes crossovers to cluster at the ends of long arms in acrocentric chromosomes, and greatly reduces crossing over on short arms. The effect of centromeres on recombination is much weaker in females. Genomic differentiation between G. aculeatus and G. nipponicus is strongly correlated with recombination rate, and patterns of differentiation along chromosomes are strongly influenced by male-specific telomere and centromere effects. We found no evidence for fine-scale correlations between recombination and local gene content in either sex. We discuss hypotheses for the origin of sexual dimorphism in recombination and its consequences for sexually antagonistic selection and sex chromosome evolution.

https://ift.tt/2Jzbu9x

Identification and validation of a 3-gene methylation classifier for HPV-based cervical screening on self-samples

Purpose: Offering self-sampling of cervico-vaginal material for high-risk human papillomavirus (hrHPV) testing is an effective method to increase the coverage in cervical screening programs. Molecular triage directly on hrHPV-positive self-samples for colposcopy referral opens the way to full molecular cervical screening. Here, we set out to identify a DNA methylation classifier for detection of cervical precancer (CIN3) and cancer, applicable to lavage and brush self-samples. Experimental Design: We determined genome-wide DNA methylation profiles of 72 hrHPV-positive self-samples, using the Infinium Methylation 450K Array. The selected DNA methylation markers were evaluated by multiplex quantitative methylation-specific PCR (qMSP) in both hrHPV-positive lavage (n=245) and brush (n=246) self-samples from screening cohorts. Subsequently, logistic regression analysis was performed to build a DNA methylation classifier for CIN3 detection applicable to self-samples of both devices. For validation, an independent set of hrHPV-positive lavage (n=199) and brush (n=287) self-samples was analyzed. Results: Genome-wide DNA methylation profiling revealed 12 DNA methylation markers for CIN3 detection. Multiplex qMSP analysis of these markers in large series of lavage and brush self-samples yielded a 3-gene methylation classifier (ASCL1, LHX8 and ST6GALNAC5). This classifier showed a very good clinical performance for CIN3 detection in both lavage (AUC=0.88; sensitivity=74%; specificity=79%) and brush (AUC=0.90; sensitivity=88%; specificity=81%) self-samples in the validation set. Importantly, all self-samples from women with cervical cancer scored DNA methylation-positive. Conclusion: By genome-wide DNA methylation profiling on self-samples, we identified a highly effective 3-gene methylation classifier for direct triage on hrHPV-positive self-samples, which is superior to currently available methods.

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Complete and durable responses in Primary Central Nervous System Post-Transplant Lymphoproliferative Disorder with Zidovudine, Ganciclovir, Rituximab and Dexamethasone

Purpose:  Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a complication of solid organ transplantation with a poor prognosis and typically associated with Epstein-Barr virus (EBV). We hypothesized EBV lytic-phase protein expression would allow successful treatment with antiviral therapy. Experimental Design:  Thirteen patients were treated with zidovudine (AZT), ganciclovir (GCV), dexamethasone, and rituximab in EBV+ PCNS-PTLD.  Twice-daily, intravenous AZT 1500 mg, GCV 5 mg/kg, and dexamethasone 10 mg were given for 14-days. Weekly Rituximab 375 mg/m2 was delivered for the first four weeks. Twice-daily Valganciclovir 450 mg and AZT 300 mg started day 15. Lytic and latent protein expression was assessed using in situ hybridization and immunohistochemistry. Immunoblot assay assessed lytic gene activation.  Cells transfected with lytic kinase vectors were assessed for sensitivity to our therapy using MTS tetrazolium and flow cytometry. Results:  The median time to response was 2 months. Median therapy duration was 26.5 months.  Median follow-up was 52 months. The estimated two-year overall survival (OS) was 76.9% (95% CI: 44.2-91.9%). Overall response rate (ORR) was 92% (95% CI: 64-100%). BXLF1/vTK and BGLF4 expression was found in the seven tumor biopsies evaluated. Lytic gene expression was induced in vitro using the four-drug regimen. Transfection with viral kinase cDNA increased cellular sensitivity to antiviral therapy. Conclusions:  EBV+ PCNS-PTLD expressed lytic kinases and therapy with AZT, GCV, rituximab and dexamethasone provided durable responses. Induction of the lytic protein expression and increased cellular sensitivity to antiviral therapy after transfection with viral kinase cDNA provides a mechanistic rationale for our approach.

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Time from Semiosis: E-series Time for Living Systems

Abstract

We develop a semiotic scheme of time, in which time precipitates from the repeated succession of punctuating the progressive tense by the perfect tense. The underlying principle is communication among local participants. Time can thus be seen as a meaning-making, semiotic system in which different time codes are delineated, each having its own grammar and timekeeping. The four time codes discussed are the following: the subjective time having tense, the objective time without tense, the static time without timekeeping, and the inter-subjective time of the E-series. Living organisms adopt a time code called the E-series, which emerges through the local synchronization among organisms or parts of organisms. The inter-subjective time is a new theoretical dimension resulting from the time-aligning activities of interacting agents. Such synchronization in natural settings consists of incessant mutual corrections and adjustments to one's own punctuation, which is then constantly updated. Unlike the third-person observer keeping the objective time while sitting outside a clock, the second-person negotiators participate in forming the E-series time by punctuating and updating the interface through which different tenses meet at the moment of "now." Although physics allows physicists to be the only interpreters, the semiotic perspective upends the physical perspective by letting local participants be involved in the interpretation of their mutual negotiations to precipitate that which is called time.

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Understanding echinocandin resistance in the emerging pathogen Candida auris [PublishAheadOfPrint]

Candida auris has emerged simultaneously on five continents as a fungal pathogen causing nosocomial outbreaks. One of the challenges in the treatment of C. auris infections is variable antifungal susceptibility profiles among clinical isolates and the development of resistance to single or multiple classes of available antifungal drugs. Here, in vitro susceptibility to echinocandin antifungal drugs and FKS1 sequencing was performed on 106 C. auris clinical isolates. Four isolates were identified as resistant to all tested echinocandins (MIC ≥ 4 mg/l) and harbored a S639F mutation in FKS1 HS1. All remaining isolates were FKS wildtype (WT) and echinocandin-susceptible with micafungin being the most potent echinocandin (MIC₅₀= 0.125 mg/l). Antifungal susceptibility testing with caspofungin was challenging due to the fact that all FKS1 WT isolates exhibited an 'Eagle effect' (also known as paradoxical growth effect), of varying intensity. To assess whether the 'Eagle effect' resulted in pharmacodynamics resistance, 8 representative isolates were evaluated for in vivo drug response in a murine model of invasive candidiasis. All isolates were susceptible to caspofungin at a human therapeutic dose, except for those harboring the S639F mutation. The data suggest that only isolates carrying mutations in FKS1 are echinocandin-resistant and that routine in vitro susceptibility testing of C. auris isolates with caspofungin by broth microdilution method should be cautiously viewed or avoided.

https://ift.tt/2HpozBC

Report of erm(B)+ Campylobacter jejuni in the United States [PublishAheadOfPrint]

Campylobacter is a leading cause of foodborne illness in the United States, causing an estimated 1.3 million illnesses annually (1)....

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Measurement of Skeletal Muscle Area Improves Estimation of Aminoglycoside Clearance Across Body Size [PublishAheadOfPrint]

A consistent approach to the dosing of aminoglycosides across the modern body size distribution has been elusive. We evaluated whether radiologically-derived measures of body composition could explain more of the inter-patient variability in aminoglycoside pharmacokinetics (PK) than standard body size metrics. This retrospective study included adult patients treated with gentamicin or tobramycin with at least three drug concentrations and computed tomography (CT) imaging available. Aminoglycoside volume and clearance (CL) estimates were computed using a two-compartment model by Bayesian analysis. Morphomic data were extracted from CT images using a custom algorithm. Bivariable and multivariable linear regression were used to assess relationships between PK parameters and covariates. A total of 335 patients were included with a median (min, max) of 4 (3, 16) aminoglycoside concentrations per patient. The median (min, max) age, height, and weight of included patients was 57 (21, 93) years, 170 (145, 203) centimeters, and 81 (42, 187) kilograms. Both standard and morphomic measures poorly explained variability in volume (R² < 0.06). Skeletal muscle area and volume explained more of the inter-patient variability in CL than weight or sex. Higher precision was observed using a modified Cockcroft-Gault equation with skeletal muscle area at L3 (R² = 0.38) or L4 (R² = 0.37) than the standard Cockcroft-Gault equation using lean (R² = 0.23), adjusted (R² = 0.23), or total body weights (R² = 0.22). These results highlight that skeletal muscle measurements from CT images obtained in the course of care can improve the precision of aminoglycoside CL estimation over current body size scalars.

https://ift.tt/2Hpovlm

Defining substrate specificity in the CTX-M family: the role of Asp240 in ceftazidime hydrolysis [PublishAheadOfPrint]

The natural diversification of CTX-M β-lactamases led to the emergence of Asp240Gly variants in the clinic that confer reduced susceptibility to ceftazidime (CAZ). In this study, we compared the impact of this substitution on CAZ and ceftazidime/avibactam (CZA) MICs against isogenic Escherichia coli strains with different porin deficiencies. Our results show a noticeable increase in CAZ resistance in clones expressing Asp240Gly-harboring CTX-M when combined with OmpF porin deficiency. Kinetic analysis revealed that the k_cat/K_m for CAZ was 5-15-fold higher for all Asp240Gly variants, but remained 200-725-fold lower than that for cefotaxime (CTX). In vitro selection of CAZ resistant clones yielded non-susceptible CTX-M-producers (MIC>16 μg/ml) only after overnight incubation; the addition of avibactam (AVI) decreased MICs to a susceptible range against these variants. In contrast, the use of CZA as a selective agent did not yield resistant clones. AVI inactivated both CTX-M-12 and CTX-M-96 with K_iapp comparable to SHV-2 and 1,000-fold greater than PER-2 and CMY-2; k₂/K for CTX-M-12 was 24- and 35-fold higher than CTX-M-96 and CTX-M-15, respectively. Molecular modelling suggests that AVI interacts similarly with CTX-M-96 and CTX-M-15. We conclude that the impact of Asp240Gly in resistance may arise when other mechanisms are also present (i.e. OmpF deficiency). Additionally, CAZ selection could favor the emergence of CAZ-resistant sub-populations. These results define the role of Asp240 and the impact of the -Gly substitution and allow us to hypothesize that the use of CZA could be an effective preventive strategy to delay the development of resistance in this family of ESBLs.

https://ift.tt/2uWsHXk

A novel polyaminocarboxylate compound to treat murine pulmonary aspergillosis by interfering with zinc metabolism [PublishAheadOfPrint]

Aspergillus fumigatus can cause pulmonary aspergillosis in immunocompromised patients and is associated with a high mortality rate due to the lack of reliable treatment options. This opportunistic pathogen requires zinc in order to grow and cause disease. Novel compounds that interfere with fungal zinc metabolism may therefore be of therapeutic interest. We screened chemical libraries containing 59223 small molecules using a resazurin assay that compared their effects on an A. fumigatus wild type strain grown under zinc-limiting conditions and on a zinc transporter knockout strain grown under zinc-replete conditions to identify compounds affecting zinc metabolism. After a first screen 116 molecules were selected whose inhibitory effect on fungal growth was further tested by using luminescence assays and hyphal length measurements to confirm their activity, as well as to toxicity assays on HeLa cells and mice. Six compounds were selected following a re-screening, two of which were pyrazolones, two were porphyrins and two were polyaminocarboxylates. All three groups showed good in vitro activity but only one of the polyaminocarboxylates was able to significantly improve the survival of immunosuppressed mice suffering from pulmonary aspergillosis. This two-tier screening approach led us to the identification of a novel small molecule with in vivo fungicidal effects and low murine toxicity that may lead to the development of new treatment options for fungal infections either by administration of this compound as a monotherapy or as part of a combination therapy.

https://ift.tt/2HpooWY

Aspergillus fumigatus cyp51A polymorphisms, an insight on their significance. [PublishAheadOfPrint]

Triazole antifungal compounds are the first treatment choice for invasive aspergillosis. However, in the last decade Aspergillus fumigatus azole resistance has increased notoriously. The main resistance mechanisms are well-defined and mostly related to point mutations of the azole target, 14-α sterol demethylase (cyp51A), with or without tandem repeat integrations in the cyp51A promoter. Furthermore, different combinations of five Cyp51A mutations (F46Y, M172V, N248T, D255E and E427K) have been reported worldwide in around 10% of the total A. fumigatus isolated. The azole susceptibility profile of these strains shows elevated azole minimum inhibitory concentrations, although based on azole susceptibility breakpoints these strains are not considered as azole resistant. The purpose of the study was to determine whether these cyp51A polymorphisms (SNPs) are responsible for the azole susceptibility profile and whether they are reflected in a poorer azole treatment response in vivo that could compromise patient treatment and outcome. A cyp51A deleted mutant was generated, becoming fully susceptible to all azoles tested. Also, three gene constructions with different combinations of cyp51A-SNPs were generated and re-introduced in an azole susceptible wild-type (WT) strain (akuB^KU80). The alternative model host Galleria mellonella was used to compare virulence and voriconazole response of infected larvae with A. fumigatus cyp51A-WT or cyp51A-SNP strains. All strains were pathogenic in G. mellonella although they did not respond similarly to voriconazole therapeutic doses. Finally, these strains were full genome sequenced and analyzed in comparison with A. fumigatus-WT strains, revealing that they belong to different strain clusters or lineages.

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Imidazopyridine compounds inhibit mycobacterial growth by depleting ATP levels [PublishAheadOfPrint]

The imidazopyridines are a promising new class of anti-tubercular agents with potent activity in vitro and in vivo. We isolated resistant mutants of Mycobacterium tuberculosis to a representative imidazopyridine; mutants had large shifts (>20-fold) in MIC (minimum inhibitory concentration). Whole genome sequencing revealed mutations in Rv1339, a hypothetical protein of unknown function. We isolated mutants to three further compounds from the series; mutants with single nucleotide polymorphisms in Rv1339 were isolated against two compounds. Mutants with single nucleotide polymorphisms in QcrB, the proposed target for this series, were isolated against one compound. All strains were resistant to two compounds, regardless of the mutation and a strain carrying the QcrB T313I mutation was resistant to all of the imidazopyridine derivatives tested, confirming cross-resistance. We confirmed that compounds from this series were targeting QcrB by monitoring pH homeostasis and ATP generation; imidazopyridines disrupted pH homeostasis and depleted ATP, providing further evidence of an effect on the electron transport chain. A representative compound was bacteriostatic against replicating bacteria, consistent with a mode of action against QcrB. The series had a narrow inhibitory spectrum, with no activity against other bacterial species. No synergy or antagonism was seen with other anti-tuberculosis drugs under development. In conclusion, our data support the hypothesis that the imidazopyridine series functions by reducing ATP generation via inhibition of QcrB.

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High levels of intrinsic tetracycline resistance in Mycobacterium abscessus is conferred by a tetracycline- modifying monooxygenase [PublishAheadOfPrint]

Tetracyclines have been one of the most successful class of antibiotics. However, its extensive use has led to the emergence of wide-spread drug resistance resulting in discontinuation of use against several bacterial infections. Prominent resistance mechanisms include drug efflux and the use of ribosome protection proteins. Infrequently, tetracyclines can be inactivated by the TetX class of enzymes, also referred to as tetracycline destructases. Low levels of tolerance to tetracycline in M. smegmatis and M. tuberculosis has been previously attributed to the WhiB7- dependent TetV/Tap efflux pump. However, M. abscessus is ~500 fold more resistant to tetracycline as compared to M. smegmatis and M. tuberculosis. In the present study, we show that this high level of resistance to tetracycline and doxycycline in M. abscessus is conferred by a WhiB7 independent tetracycline inactivating monooxygenase, MabTetX (MAB_1496c). Presence of sublethal doses of tetracycline and doxycycline results in >200-fold induction of MabTetX and an isogenic deletion strain is highly sensitive to both antibiotics. Further, purified MabTetX can rapidly monooxygenate both antibiotics. We also demonstrate that expression of MabTetX is repressed by MabTetR_x, by binding to an inverted repeat sequence upstream of MabTetR_x; presence of either antibiotic relieves this repression. Moreover, anhydrotetracycline (ATc) can effectively inhibit MabTetX activity in vitro and decreases the MIC of both tetracycline and doxycycline in vivo. Finally, we show that tigecycline, a third-generation tetracycline, is not only a poor substrate of MabTetX, but is also incapable of inducing the expression of MabTetX. This is the first demonstration of a tetracycline inactivating enzyme in mycobacteria. It a) elucidates the mechanism of tetracycline resistance in M. abscessus, 2) demonstrates the use of an inhibitor that can potentially reclaim the use of tetracycline and doxycycline and 3) identifies two sequential bottlenecks — MabTetX and MabTetR_x — for acquiring resistance to tigecycline thereby reiterating its use against M. abscessus.

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Polymyxin B in Combination with Enrofloxacin Exerts Synergistic Killing against Extensive Drug-resistant Pseudomonas aeruginosa [PublishAheadOfPrint]

Polymyxins are increasingly used as a last-resort class of antibiotics against extensive drug-resistant (XDR) Gram-negative bacteria. However, resistance to polymyxins can emerge with monotherapy. As nephrotoxicity is the major dose-limiting factor for polymyxin monotherapy, dose escalation to suppress the emergence of polymyxin resistance is not a viable option. Therefore, novel approaches are needed to preserve this last-line class of antibiotics. This study aimed to investigate the antimicrobial synergy of polymyxin B combined with enrofloxacin against Pseudomonas aeruginosa. Static time-kill studies were conducted over 24 h with polymyxin B (1-4 mg/L) and enrofloxacin (1-4 mg/L) alone or in combination. Additionally, a one-compartment in vitro model (IVM) and hollow-fiber infection model (HFIM) was performed against P. aeruginosa 12196. Polymyxin B and enrofloxacin in monotherapy were ineffective against all of the P. aeruginosa isolates examined. Whereas, polymyxin B-enrofloxacin in combination was synergistic against P. aeruginosa with ≥ 2-4 log₁₀ kill at 24 h in the static time-kill studies. In both IVM and HFIM, the combination was synergistic and the bacterial counting values were below the limit of quantification on day 5 in the HFIM. A population analysis profile indicated that the combination inhibited the emergence of polymyxin resistance in P. aeruginosa 12196. The mechanism-based modeling suggests that the synergistic killing is a result of the combination of mechanistic and subpopulation synergy. Overall, this is the first preclinical study to demonstrate that the polymyxins-enrofloxacin combination is of considerable utility for the treatment of XDR P. aeruginosa infections and warrants future clinical evaluations.

https://ift.tt/2Hpog9W

Alterations of metabolic and lipid profiles in polymyxin-resistant Pseudomonas aeruginosa [PublishAheadOfPrint]

Multidrug-resistant Pseudomonas aeruginosa presents a global medical challenge and polymyxins are a key last-resort therapeutic option. Unfortunately, polymyxin resistance in P. aeruginosa has been increasingly reported. The present study was designed to define metabolic differences between paired polymyxin-susceptible and -resistant P. aeruginosa strains using untargeted metabolomics and lipidomics analyses. The metabolomes of wild-type PAK (polymyxin B MIC 1 mg/L) and its paired pmrB mutant strains, PAKpmrB6 and PAKpmrB12 (polymyxin B MICs 16 mg/L and 64 mg/L, respectively) were characterized using liquid chromatography-mass spectrometry, and metabolic differences were identified through multivariate and univariate statistics. PAKpmrB6 and PAKpmrB12 which displayed lipid A modification with 4-amino-4-deoxy-L-arabinose showed significant perturbations in amino acid and carbohydrate metabolism, particularly intermediate metabolites from 4-amino-4-deoxy-L-arabinose synthesis and the methionine salvage cycle pathways. Genomics result showed a premature termination (Y275stop) in speE (encoding spermidine synthase) in PAKpmrB6 and metabolomics data revealed a decreased intracellular level of spermidine in PAKpmrB6 compared to PAKpmrB12. Our results indicate that spermidine may play an important role in high-level polymyxin resistance in P. aeruginosa. Interestingly, both pmrB mutants had decreased levels of phospholipids, fatty acids and acyl-coenzyme A compared to the wild-type PAK strain. Moreover, the more resistant PAKpmrB12 mutant exhibited much lower levels of phospholipids than the PAKpmrB6 mutant, suggesting the decreased phospholipid level was associated with polymyxin resistance. In summary, this study provides novel mechanistic information on polymyxin resistance in P. aeruginosa and highlights its impacts on bacterial metabolism.

https://ift.tt/2uZ31JM

Hiding in Plain Sight: Rediscovering the Importance of Noncoding RNA in Human Malignancy

At the time of its construction in the 1950s, the central dogma of molecular biology was a useful model that represented the current state of knowledge for the flow of genetic information after a period of prolific scientific discovery. Unknowingly, it also biased many of our assumptions going forward. Whether intentional or not, genomic elements not fitting into this paradigm were deemed unimportant and emphasis on the study of protein-coding genes prevailed for decades. The phrase "Junk DNA," first popularized in the 1960s, is still used with alarming frequency to describe the entirety of noncoding DNA. It has since become apparent that RNA molecules not coding for protein are vitally important in both normal development and human malignancy. Cancer researchers have been pioneers in determining noncoding RNA function and developing new technologies to study these molecules. In this review, we will discuss well known and newly emerging species of noncoding RNAs, their functions in cancer, and new technologies being utilized to understand their mechanisms of action in cancer. Cancer Res; 1–10. ©2018 AACR.

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Informal CVD Caregiving Costs Estimated at $61 Billion in 2015

MONDAY, April 9, 2018 -- The costs of informal caregiving for patients with cardiovascular disease (CVD) were estimated at $61 billion in 2015 and are set to more than double by 2035, according to a policy statement published online April 9 in...

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Cannabis Compound Transfers to Breast Milk

MONDAY, April 9, 2018 -- Low concentrations of delta-9-tetrahydrocannabinol are transferred from inhaled cannabis to breast milk of women who regularly consume cannabis, according to a study published online April 9 in Obstetrics &...

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Prenatal Exposure to SSRI Tied to Fetal Brain Development

MONDAY, April 9, 2018 -- Prenatal exposure to a selective serotonin reuptake inhibitor (SSRI) is associated with fetal brain development, according to a study published online April 9 in JAMA Pediatrics. Claudia Lugo-Candelas, Ph.D., from the...

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Sirolimus May Be Beneficial in DIPNECH Syndrome

MONDAY, April 9, 2018 -- Sirolimus may be beneficial for patients with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH), according to a research letter published online April 10 in the Annals of Internal Medicine. Sylvain...

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Pharmacists Play Role in Cutting Hospital-Acquired Infections

MONDAY, April 9, 2018 -- Pharmacists have been involved in the recent progress made toward reducing hospital-acquired infections (HAIs), according to an article published in Drug Topics. According to the latest data from the U.S. Centers for Disease...

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Common Hepatic Duct Stricture Due to Surgical Clip

An 84-year-old Caucasian man came in for follow-up endoscopic retrograde cholangiopancreatography (ERCP). He had been diagnosed with choledocholithiasis 6 months ago, which was treated with an ERCP and placement of a 10F × 7-cm plastic stent in the common bile duct. It was followed by a laparoscopic cholecystectomy a month later. An ERCP was performed after the cholecystectomy for stent removal, which showed stricture in the common hepatic duct (CHD). A repeat 10F × 7-cm plastic stent was placed during the procedure and brushings for cytology were negative.

https://ift.tt/2H5NLQb

Choledochoduodenal Fistula Secondary to Ulcer Disease Presenting With Gastrointestinal Bleeding

An 84-year-old woman presented with hematemesis and epigastric pain. Her medical history was notable for a cerebrovascular accident, and she was taking aspirin and nonsteroidal anti-inflammatory drugs. Her serum hemoglobin level decreased to 6.7 g/dL (range, 11–17 g/dL), and her blood urea nitrogen level increased to 107 mg/dL (range, 17–43 mg/dL). An esophagogastroduodenoscopy (EGD) was performed, which showed a large duodenal ulcer (DU) with an adherent clot and an orifice suggestive of perforation (Figure A).

https://ift.tt/2IGwgTL

The Rusty Ring Sign Streamlining Flat Lesion Detection in Subtle Melanosis Coli

A 59-year-old man with regular on-demand laxative use underwent a screening colonoscopy (EC-760R-V/I; Fujinon, Düsseldorf, Germany). The entire mucosa was noted for speckled fine brown pigment spots consistent with discrete melanosis coli. In the descending colon, there was a brownish ring structure that was noticeable in the first instance, encircling a flat depigmented patch lesion (Paris 0–IIa) estimated at 3 mm (Figure A). Linked color imaging likewise highlighted the avascular nature of the lesion and indicated a fine granular mucosal surface pattern (Figure B).

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Laparoscopic excision of deep rectovaginal endometriosis in BSGE endometriosis centres: a multicentre prospective cohort study

Objective

To estimate the effectiveness and safety of laparoscopic surgical excision of rectovaginal endometriosis.

Design

A multicentre, prospective cohort study.

Setting

51 hospitals accredited as specialist endometriosis centres.

Participants

5162 women of reproductive age with rectovaginal endometriosis of which 4721 women had planned laparoscopic excision.

Interventions

Laparoscopic surgical excision of rectovaginal endometriosis requiring dissection of the pararectal space.

Main outcome measures

Standardised symptom questionnaires enquiring about chronic pelvic pain, bladder and bowel symptoms, analgesia use and quality of life (EuroQol) completed prior to surgery and at 6, 12 and 24 months postoperatively. Serious perioperative and postoperative complications including major haemorrhage, infection and visceral injury were recorded.

Results

At 6 months postsurgery, there were significant reductions in premenstrual, menstrual and non-cyclical pelvic pain, deep dyspareunia, dyschezia, low back pain and bladder pain. In addition, there were significant reductions in voiding difficulty, bowel frequency, urgency, incomplete emptying, constipation and passing blood. These reductions were maintained at 2 years, with the exception of voiding difficulty. Global quality of life significantly improved from a median pretreatment score of 55/100 to 80/100 at 6 months. There was a significant improvement in quality of life in all measured domains and in quality-adjusted life years. These improvements were sustained at 2 years. All analgesia use was reduced and, in particular, opiate use fell from 28.1% prior to surgery to 16.1% at 6 months. The overall incidence of complications was 6.8% (321/4721). Gastrointestinal complications (enterotomy, anastomotic leak or fistula) occurred in 52 (1.1%) operations and of the urinary tract (ureteric/bladder injury or leak) in 49 (1.0%) procedures.

Conclusion

Laparoscopic surgical excision of rectovaginal endometriosis appears to be effective in treating pelvic pain and bowel symptoms and improving health-related quality of life and has a low rate of major complications when performed in specialist centres.

https://ift.tt/2qopXgX

FDA Restricts Sale and Distribution of Essure to Protect Women and to Require that Patients Receive Risk Information

April 9, 2018 -- The U.S. Food and Drug Administration today issued an order to restrict the sale and distribution of the Essure device to ensure that all women considering use of the permanent contraception device are provided with adequate risk...

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Recommendations for evaluation and management of pain in patients with mucopolysaccharidosis in Latin America

The mucopolysaccharidosis (MPS) constitute a heterogeneous group of rare genetic disorders caused by enzymatic deficiencies that lead to the accumulation of glycosaminoglycans (GAGs). Several types of MPS are described, historically numbered from I to IX. Clinical observations strongly suggest the presence of chronic pain in patients with all types of MPS. There are few data in the literature on the evaluation and management of pain in these patients, a fact which can compromise the quality of life even more.

https://ift.tt/2ExyXo0

Designed Learning: Missing Data in Clinical Research

Handling of missing data in clinical trials is often suboptimal. One solution could involve creating new mechanisms to deliver the information directly to the communities of scientists at the front lines. In our continued effort to explain analytic methods to clinical researchers in new ways, Annals joined forces with Sense About Science USA to communicate concepts of missing data through graphic design.

https://ift.tt/2EyJyin

U.S. Food and Drug Administration Precertification Pilot Program for Digital Health Software: Weighing the Benefits and Risks

In 2017, the U.S. Food and Drug Administration (FDA) announced a new program for software classified as a medical device. The Digital Health Software Precertification (Pre-Cert) Program is designed to expedite regulatory review for companies that demonstrate quality and organizational excellence in software development. Although Pre-Cert is intended to promote the worthy goals of access and innovation in digital health, many questions have been raised. In particular, Pre-Cert may reduce incentives for developers to study the safety and effectiveness of their software products before patients start to rely on them. Although postmarket surveillance can mitigate risks of these products, the FDA does not have as much authority after a product's widespread use to enforce data collection deadlines. Pre-Cert may also create confusion for patients and physicians, who may believe that marketed products were subject to rigorous study.

https://ift.tt/2Jv2ouC

We Should Measure What Matters in Bundled Payment Programs

The Merit-based Incentive Payment System provides for new ways to pay for care, including bundled payment programs, which pay a fixed amount for the total cost of care during a defined period surrounding a procedure. Quality measures were defined for these bundles to encourage appropriate care and discourage underuse of needed services. The authors detail the ways in which current measures fail to adequately measure the quality of health care and describe a framework for improving these measures.

https://ift.tt/2IFNEb6

The Effect of Telehealth on Spending: Thinking Through the Numbers

The virtual and remote technologies that we call telehealth are changing the availability and cost of health care. Telehealth can often be provided at a lower cost than other types of care, but it may increase the total amount of care delivered. The effect on spending depends on how much telehealth substitutes for other types of care, and how much it adds to the overall volume of care. This article explains the various mechanisms by which telehealth can affect this spending equation.

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Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia Syndrome Treated With Sirolimus

https://ift.tt/2IHz1E9

Standalone cranio-cervical decompression is feasible in children with mucopolysaccharidosis type I, IVA and VI

Publication date: Available online 9 April 2018
Source:The Spine Journal
Author(s): Harald Krenzlin, Ta-Chih Tan, Christina Lampe, Christian Lampe, Markus Knuf, Peter Horn, Manfred Schwarz
Background contextIn patients with Mucopolysaccharidosis (MPS), glycosaminoglycans deposits in the dura mater and supporting ligaments cause spinal cord compression and consecutive myelopathy, predominantly of the cranio-cervical junction. Disease characteristics of cranio-cervical stenosis (CCS) in MPS patients differ profoundly from other hereditary and degenerative forms.Due to high peri-procedural morbidity and mortality, MPS patients pose a substantial challenge to the unexperienced medical care provider. As literature remains scarce, we present our experience with a large cohort of MPS patients treated for CCS without atlanto-occiptal instrumentation.PurposeTo describe a save and least traumatic approach for treating CCS in children with MPS, avoiding primary instrumentation.Study designThis is a prospective follow-up (cohort) study.Patient samplesWe report 15 consecutive patients with CCS related to MPS, which were treated with standalone cervical decompression.Outcome measuresMyelopathy was assessed using MRI, somatosensory evoked potentials and clinical evaluation. Cervical instability was evaluated using plain x-ray and MRI. The disability status is quantified using either the Karnofsky- or Lansky Performance score.MethodsWe describe 15 consecutive patients treated with cranio-cervical decompression. Data was collected prospectively. The mean follow-up is 6 years (SD 5). The technique and treatment principles are described.ResultsThe overall clinical outcome in this patient cohort is good (mean Karnofsky Performance Score 80). No patient developed signs of C0-C1-C2 instability or progressive myelopathy. Re-stenosis occurred in 7 patients requiring a total of 8 re-operations.ConclusionsSurgery in patients with MPS is associated with high morbidity and a mortality of up to 4.2 %. Due to the unique nature of the disease, recurring stenosis is inevitable. In order to shorten the procedure time and simplify the anticipated re-operation, we provide data that cranio-cervical decompression is feasible without the necessity of primary osteosynthesis. In the absence of cranio-cervical instability, decompression surgery without occipito-cervical stabilisation yields good postoperative results and challenges the long-standing paradigm of prophylactic cranio-cervical fixation.



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Evaluating the effect of growing patient numbers and changing data elements in the national surgical quality improvement program (NSQIP) database over the years: a study of posterior lumbar fusion outcomes

Publication date: Available online 9 April 2018
Source:The Spine Journal
Author(s): B.N. Shultz, P. Bovonratwet, N.T. Ondeck, T.D. Ottesen, R.P. McLynn, J.N. Grauer
Background ContextThe use of national databases in spinal surgery outcomes research is increasing. A number of variables collected by the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) changed between 2010 and 2011, coinciding with a rapid increase in the number of patients included per year. However, there has been limited study evaluating the effect that these changes may have on the results of outcomes studies.PurposeTo investigate the influence of changing data elements and growth of the NSQIP database on results of lumbar fusion outcomes studies.Study Design/SettingRetrospective cohort study of prospectively collected data.Patient SampleThe NSQIP database was retrospectively queried to identify 19,755 patients who underwent elective posterior lumbar fusion surgery +/- interbody fusion between 2005 and 2014. Patients were split into two groups based on year of surgery: 2,802 from 2005-2010 and 16,953 from 2011-2014.Outcome MeasuresThe occurrence of adverse events after discharge from the hospital, within postoperative day 30.MethodsPreoperative characteristics and 30-day perioperative outcomes were compared between the era groups using bivariate analysis. To illustrate the effect of such changing data elements, the association between age and postoperative outcomes in the era groups was analyzed using multivariate Poisson regression. The current study had no funding sources, and there were no study-related conflicts of interest for any authors.ResultsThere were significant differences between the era groups for a variety of preoperative characteristics. Postoperative events such blood transfusion and deep vein thrombosis were also significantly different between the era groups. For the 2005-2010 cohort, age was significantly associated with septic shock by multivariate analysis. For the 2011-2014 cohort, age was significantly associated with septic shock, urinary tract infection, blood transfusion, myocardial infarction, and extended length of stay.ConclusionsThe NSQIP database has undergone substantial changes between 2005 and 2014. These changes may contribute to different results in analyses, such as the association between age and postoperative outcomes, when using older versus newer data. Conclusions from early studies using this database may warrant reconsideration.



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Missing data treatments matter: an analysis of multiple imputation for anterior cervical discectomy and fusion procedures

Publication date: Available online 9 April 2018
Source:The Spine Journal
Author(s): Nathaniel T. Ondeck, Michael C. Fu, Laura A. Skrip, Ryan P. McLynn, Jonathan J. Cui, Bryce A. Basques, Todd J. Albert, Jonathan N. Grauer
BACKGROUND CONTEXTThe presence of missing data is a limitation of large datasets, including the National Surgical Quality Improvement Program (NSQIP). In addressing this issue, most studies utilize complete case analysis, which excludes cases with missing data, thus potentially introducing selection bias. Multiple imputation, a statistically rigorous approach that approximates missing data and preserves sample size, may be an improvement over complete case analysis.PURPOSETo evaluate the impact of using multiple imputation in comparison to complete case analysis for assessing the associations between preoperative laboratory values and adverse outcomes following anterior cervical discectomy and fusion (ACDF) procedures.STUDY DESIGN/SETTINGRetrospective review of prospectively collected dataPATIENT SAMPLEPatients undergoing one-level ACDF were identified in NSQIP 2012-2015.OUTCOME MEASURESPerioperative adverse outcome variables assessed included the occurrence of any adverse event, severe adverse events, and hospital readmission.METHODSMissing preoperative albumin and hematocrit values were handled using complete case analysis and multiple imputation. These preoperative laboratory levels were then tested for associations with 30-day postoperative outcomes using logistic regression.RESULTSA total of 11,999 patients were included. Of this cohort, 63.5% of patients were missing preoperative albumin and 9.9% were missing preoperative hematocrit.When utilizing complete case analysis, only 4,311 patients were studied. The removed patients were significantly younger, healthier, of a common BMI and male. Logistic regression analysis failed to identify either preoperative hypoalbuminemia or preoperative anemia as significantly associated with adverse outcomes.When employing multiple imputation, all 11,999 patients were included. Preoperative hypoalbuminemia was significantly associated with the occurrence of any adverse event and severe adverse events. Preoperative anemia was significantly associated with the occurrence of any adverse event, severe adverse events, and hospital readmission.CONCLUSIONMultiple imputation is a rigorous statistical procedure that is being increasingly used to address missing values in large datasets. Utilizing this technique for ACDF avoided the loss of cases that may have affected the representativeness and power of the study and led to different results than complete case analysis. Multiple imputation should be considered for future spine studies.



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Anxiety and depression in spine surgery – a systematic integrative review

Publication date: Available online 9 April 2018
Source:The Spine Journal
Author(s): Janni Strøm, Merete B. Bjerrum, Claus V. Nielsen, Cecilie N. Thisted, Tove L. Nielsen, Malene Laursen, Lene B. Jørgensen
BackgroundSymptoms of preoperative anxiety and depression occur in approximately one-third of patients with chronic back pain undergoing surgery. In the last 2 decades, several studies have established that preoperative anxiety and depression are important outcome predictors of greater pain and physical impairments, and lower health-related quality of life in patients undergoing spine surgery. To accommodate symptoms of anxiety and depression and thereby better surgical outcomes, we need to identify factors associated with these symptoms.PurposeTo identify factors associated with symptoms of anxiety and depression in adults both before and after undergoing spinal surgery.Study designIntegrative literature reviewMethodsThe independent charity Helsefonden supported this literature review by contributing $45,000 to remunerate a dedicated investigator. A systematic literature search was conducted in PubMed, CINAHL, PsycINFO, Embase, Scopus, Cochrane, and Web of Science. A three-step selection and assessment process was conducted; titles and abstracts of 1124 articles were skimmed for relevance, of these 53 articles were found to be of relevance and were read in full. Articles not meeting the inclusion criteria (n=26) were excluded. The 31 articles were critically appraised for methodological validity; 14 of these were synthesized and analyzed using a convergent qualitative design to transform both qualitative and quantitative articles into qualitative findings.ResultsFourteen studies were included, reporting results based on 4,833 participants, 3,017 males and 1,816 females, whose mean age was approximately 49 years. From these results, we extracted 75 individual findings, which we then divided into five categories of factors associated with anxiety and depression both before and after undergoing spine surgery: pain, information, disability, employment, and mental health.ConclusionsFive categories of interacting factors that influenced symptoms of anxiety and depression both before and after surgery were identified: pain, lack of information, disability, return to work, and mental health. Information appears to have a regulating effect on anxiety and depression.



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Independent predictors of spinal epidural abscess recurrence

Publication date: Available online 9 April 2018
Source:The Spine Journal
Author(s): Akash A. Shah, Huiliang Yang, Paul T. Ogink, Joseph H. Schwab
Background contextRecurrence of spinal epidural abscess (SEA) after treatment is an important cause of continued morbidity for patients.PurposeThe purpose of this study is to identify independent predictors of recurrence of SEA.Study design/settingThis was a retrospective, case-control study.Patient samplePatients 18 years or older with a diagnosis of SEA admitted to our hospital system during the study period were included in the study sample.Outcome measuresThe outcome measure was recurrence of SEA, defined as a re-accumulation of pus or infected granulation tissue in the epidural space after initial treatment.MethodsAll patients older than 18 years admitted to our hospital system with a diagnosis of SEA from 1993 to 2016 were identified, and explanatory variables and outcomes were collected retrospectively. Patients 18 years or older diagnosed with SEA were included. We excluded patients whose treatment was initiated at an outside institution. Bivariate and multivariate analyses were performed to identify independent predictors of recurrence.ResultsWe identified 1,053 patients with SEA. We only considered patients to be recurrence-free if they had no documented recurrence with greater than 20 weeks of follow-up. Five hundred and thirty-four patients were recurrence-free and 38 had documented recurrence, yielding 572 patients who were included in this analysis. Bivariate and multivariate analyses identified three independent predictors of recurrence: history of intravenous drug use, fecal incontinence/retention, and local spinal wound infection.ConclusionsPatients with SEA who have a history of intravenous drug use, bowel dysfunction at presentation, and/or concurrent local spinal wound infection are at increased risk of disease recurrence. These patients ought to be closely followed after discharge, with frequent serial imaging and aggressive antibiotic treatment.



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Surgical treatment improves survival of elderly with axis fracture – a national population-based multi-registry cohort study

Publication date: Available online 9 April 2018
Source:The Spine Journal
Author(s): Anna-Lena Robinson, Claes Olerud, Yohan Robinson
Background ContextFractures of the axis (C2) are the most common cervical spinal injuries in the elderly population. Several authors have reported improved survival among elderly patients with C2 fractures when treated surgically.PurposeTo analyze whether surgery improves survival of elderly with C2 fractures.Study Design/ SettingObservational population-based longitudinal multi-registry studyPatient SampleSwedish Patient Registry 1997 to 2014, and Swedish Cause of Death Registry 1997 to 2014Outcome measuresSurvival after C2 fracture according to non-surgical and surgical treatment.MethodsIncluded were all patients treated for the primary diagnosis of C2 fracture (ICD-10: S12.1) at an age ≥70 years, receiving treatment at a healthcare facility. Non-surgical treatment comprises of cervical collar or halo-vest treatment. Surgical treatment was identified in the Swedish patient registry extract using the Swedish classification of procedural codes. Survival was determined using the Kaplan Meier method. Comorbidity was determined using the Charlson Comorbidity Index.ResultsOf the included 3,375 elderly patients with C2 fractures (43% male, aged 83±7 years), 22% were treated surgically. Surgical treatment was assigned based on age, gender and year of treatment. The one-year survival of 2,618 non-surgically treated patients was 72% (n=1,856), and 81% (n=614) for the 757 surgically treated (p<0.001, RRR=11%). Adjusted for age, gender, comorbidity and year of injury, surgically treated patients had greater survival than non-surgically treated patients (HR=0.88, 95% CI: 0.79-0.97). Among those above 88 years of age (95% CI: 85-92), surgical treatment lost its effect on survival.ConclusionsDespite the frailty of elderly patients, the morbidity of cervical external immobilization with a rigid collar seemingly weighs greater than surgical morbidity, even in octogenarians. For those above 88 years of age, non-surgical treatment should be primarily attempted.Trial registrationClinicalTrials.gov #NCT02839057



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Predictors of adverse discharge disposition in adult spinal deformity and associated costs

Publication date: Available online 9 April 2018
Source:The Spine Journal
Author(s): Peter G. Passias, Gregory W. Poorman, Cole A. Bortz, Rabia Qureshi, Bassel G. Diebo, Justin C. Paul, Samantha R. Horn, Frank A. Segreto, Alexandra Pyne, Cyrus M. Jalai, Virginie Lafage, Shay Bess, Frank J. Schwab, Hamid Hassanzadeh
Background ContextWith advances in the understanding of adult spinal deformity (ASD), more complex osteotomy and fusion techniques are being implemented with increasing frequency. Patients undergoing ASD corrections infrequently require extended acute care, longer inpatient stays, and are discharged to supervised care. Given the necessity of value-based health care, identification of clinical indicators for adverse discharge disposition in ASD surgeries is paramount.PurposeOn nationwide and surgeon-created databases, identify predictors of adverse discharge disposition after ASD surgeries and view corresponding differences in charges.Study Design/SettingRetrospective analysis of patients on the National Surgical Quality Improvement Program (NSQIP) database and cost data from Medicare PearlDiver Database.Patient SamplePatients undergoing thoracolumbar surgery for correction of ASD.Outcome MeasuresPrimary: Discharge disposition home vs. not home. Secondary: Cost differences across discharge groups.MethodsPatients on NSQIP undergoing thoracolumbar ASD-corrective surgery with a primary diagnosis of scoliosis (ICD-9 code 737.x), and over the age of 18 were isolated. Predictors (demographic, clinical, and complications) of not-home (NH; rehab or skilled nursing facility) discharge were analyzed using binary logistic regression controlling for levels fused, decompressions, osteotomies, and revisions. Average 30-day and 90-day costs of care were reported in home, rehab, and skilled nursing facility discharge groups in patients undergoing 8+ level thoracolumbar fusion.Results1,978 patients undergoing lumbar ASD-corrective surgery were included for analysis (average age: 59.3 years, sex: 64% female). Average length of stay was 6.58 days. Upon multivariate regression analysis, age over 60 years (OR: 0.28 CI: 0.22-0.34) and female sex (p=0.003) were independent predictors of adverse discharge status. Partially dependent pre-operational functional status, defined as reliance on another person to complete some activities of daily living, increased likelihood of adverse discharge disposition (OR:0.57 CI:0.35-0.90). Despite controlling for all clinical variables except for the ones specific to each analysis, Smith-Petersen osteotomy (OR:0.51 CI:0.40-0.64), interbody device placement (OR:0.80 CI:0.64-0.98) and fixation to the iliac (OR:0.54 CI:0.41-0.70) both increased likelihood of adverse discharge. Complications most associated with adverse discharge were UTIs (OR:0.34 CI:0.21-0.57) and blood transfusions (OR:0.42 CI:0.34-0.52). Relative to home-discharge, 30-day costs of care were +$21,061 more expensive in rehab discharges, but not different in skilled nursing facility discharges (+$5,791, p=0.177). 90-day costs of care were $23,815 in rehab discharges (p<0.001), but again not different in skilled nursing facility discharges (+$6,091, p=0.212).ConclusionsDischarge destination to rehabilitation has a significant impact on cost of thoracolumbar adult spinal deformity surgeries. Patient selection can predict patients at higher risk for discharges to rehab or skilled nursing facility.



https://ift.tt/2qidon1

Joint Laxity in Preschool Children Born Preterm

To evaluate the prevalence of joint laxity in children born preterm assessed in the first 2 years, the relationship between joint laxity and motor performance at preschool age, and possible changes over time in a subgroup of children followed longitudinally.

https://ift.tt/2GKVFPw

Pulmonary Vein Stenosis in Infants: A Systematic Review, Meta-Analysis, and Meta-Regression

To quantify outcomes of infants (<1 year of age) diagnosed with pulmonary vein stenosis (PVS).

https://ift.tt/2qiWCUc

Elucidation of the Anatomical Mechanism of Nodal Skip Metastasis in Superficial Thoracic Esophageal Squamous Cell Carcinoma

Abstract

Background

Lymph node metastasis (LNM) is a standard mechanism of cancer progression in esophageal squamous cell carcinoma (ESCC). We aimed to clarify the anatomical mechanism of skip nodal metastasis to mediastinal zones by analyzing the relationship between LNM to sentinel zones and lymphatic vessel counts in the muscle layer adjacent to the outer esophagus.

Methods

We examined the surgical records of 287 patients with ESCC who underwent potentially curative surgery (three-field lymphadenectomy) and whole esophagi, including pharynges and stomachs from 10 cadavers, to determine the number of lymphatic vessels in the intra-outer longitudinal muscle layer adjacent to the outer esophagus of the cervical (Ce), upper thoracic, middle thoracic (Mt), lower thoracic (Lt), and abdominal esophagi (Ae).

Results

The frequency of LNM to the middle mediastinal and supraclavicular zones, including the Mt and Ce, respectively, was lower than to the upper and lower mediastinal and abdominal zone in patients with superficial and advanced thoracic ESCC. In cadavers, the lymphatic vessel counts of the intra-outer longitudinal muscle layer in the Mt and Ce were significantly lower than those of the Lt and Ae, suggesting that lymphatic flow toward the outside of the Mt and Ce was not more abundant than to other sites.

Conclusion

Our anatomical data suggested that the absence of intra-muscle lymphatic vessels in the middle mediastinal and supraclavicular zones causes skip LNM in patients with thoracic ESCC. Thus, standard esophagectomy with lymph node dissection, including distant zones, may be appropriate for treating patients with superficial thoracic ESCC.

https://ift.tt/2EyAcTM

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases From a Small Bowel Adenocarcinoma: Multi-Institutional Experience

Abstract

Background

The multi-institutional registry in this study evaluated the outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases (PM) from small bowel adenocarcinoma (SBA).

Methods

A multi-institutional data registry including 152 patients with PM from SBA was established. The primary end point was overall survival (OS) after CRS plus HIPEC.

Results

Between 1989 and 2016, 152 patients from 21 institutions received a treatment of CRS plus HIPEC. The median follow-up period was 20 months (range 1–100 months). Of the 152 patients, 70 (46.1%) were women with a median age of 54 years. The median peritoneal cancer index (PCI) was 10 (mean 12; range 1–33). Completeness of cytoreduction (CCR) 0 or 1 was achieved for 134 patients (88.2%). After CRS and HIPEC, the median OS was 32 months (range 1–100 months), with survival rates of 83.2% at 1 year, 46.4% at 3 years, and 30.8% at 5 years. The median disease-free survival after CCR 0/1 was 14 months (range 1–100 months). The treatment-related mortality rate was 2%, and 29 patients (19.1%) experienced grades 3 or 4 operative complications. The period between detection of PM and CRS plus HIPEC was 6 months or less (P = 0.008), and multivariate analysis identified absence of lymph node metastasis (P = 0.037), well-differentiated tumor (P = 0.028), and PCI of 15 or lower (P = 0.003) as independently associated with improved OS.

Conclusion

The combined treatment strategy of CRS plus HIPEC achieved prolonged survival for selected patients who had PM from SBA with acceptable morbidity and mortality.

https://ift.tt/2Jy3PZs

Reasons Associated with Total Thyroidectomy as Initial Surgical Management of an Indeterminate Thyroid Nodule

Abstract

Background

Diagnostic hemithyroidectomy (HT) is the most widely recommended surgical procedure for a nodule with indeterminate cytology; however, additional details may make initial total thyroidectomy (TT) preferable. We sought to identify patient-specific factors (PSFs) associated with initial TT in patients with indeterminate thyroid nodules.

Methods

Retrospective analysis of all patients with a thyroid nodule ≥ 1 cm and initial cytology of atypia of undetermined significance or suspicious for follicular neoplasm between 2012 and 2015 who underwent thyroidectomy. Medical records were reviewed for patient demographics, neck symptoms, nodule size, cytology, molecular test results, final histopathology, and additional PSFs influencing surgical management. Variables were analyzed to determine associations with the use of initial TT. Logistic regression analyses were performed to identify independent associations.

Results

Of 325 included patients, 182/325 (56.0%) had HT and 143/325 (44.0%) had TT. While patient age and sex, nodule size, and cytology result were not associated with initial treatment, five PSFs were associated with initial TT (p < 0.0001). These included contralateral nodules, hypothyroidism, fluorodeoxyglucose avidity on positron emission tomography scan, family history of thyroid cancer, and increased surgical risk. At least one PSF was present in 126/143 (88.1%) TT patients versus 47/182 (25.8%) HT patients (p < 0.0001). Multivariate logistic regression analysis demonstrated that these variables were the strongest independent predictor of TT (odds ratio 45.93, 95% confidence interval 18.80–112.23, p < 0.001).

Conclusions

When surgical management of an indeterminate cytology thyroid nodule was performed, several PSFs were associated with a preference by surgeons and patients for initial TT, which may be useful to consider in making decisions on initial operative extent.

https://ift.tt/2IHfFz7

Single-Axillary-Incision Endoscopic-Assisted Hybrid Technique for Nipple-Sparing Mastectomy: Technique, Preliminary Results, and Patient-Reported Cosmetic Outcome from Preliminary 50 Procedures

Abstract

Background

A new hybrid technique for single-axillary-incision endoscopic-assisted nipple-sparing mastectomy (E-NSM) was introduced. Preliminary results are reported.

Methods

Patients who received single-axillary-incision E-NSM from August 2013 to August 2017 were searched from a single institution. Data were analyzed to determine the effectiveness and oncologic safety of single-axillary-incision E-NSM. Patient-oriented cosmetic outcome report was also obtained.

Results

During the study period, a total of 50 E-NSM with single-incision procedures were performed in 41 female patients with breast cancer, including 11 (26.8%) patients with bilateral disease. Their mean age was 45.3 ± 8.4 years. The mean size of tumors encountered during the 50 single-incision E-NSM procedures was 2.3 ± 1.8 (0.1–7.3) cm for invasive tumors and 2.6 ± 1.7 (0.2–5.7) cm for carcinoma in situ lesions. Six (12%) of those tumors were multifocal/multicentric. Lymph node metastasis was found during 12% of the procedures. Forty-five (90%) received immediate breast reconstruction with gel implant. Mean operating time was 244.3 ± 82.8 min. The overall complication rate was 6%, and no total nipple necrosis or implant loss was observed. No locoregional recurrence or distant metastasis was found during mean follow-up of 21.6 months. About 94.4% of patients were satisfied with the postoperative scar location and wound length. All patients who responded would choose the same operation again.

Conclusions

The proposed single-axillary-incision endoscopic hybrid technique for nipple-sparing mastectomy was a safe procedure with low morbidity and associated with high patient satisfaction.

https://ift.tt/2Jy3Jky

Predicting Survival and Response to Treatment in Gastroesophageal Neuroendocrine Tumors: An Analysis of the National Cancer Database

Abstract

Background

Neuroendocrine tumors (NETs) of the esophagus and stomach are rare neoplasms with variable behavior. We aim to describe their epidemiology and response to treatment.

Methods

NETs of the stomach and the esophagus were selected from the National Cancer Database (2004–2013) and classified by location. Survival analyses were performed with respect to tumor characteristics and treatment variables.

Results

NETs of the stomach (n = 2700; 92.8%) and esophagus (n = 210, 7.2%) were identified. Gastric cardia NETs had demographics and behavior similar to esophageal tumors and were associated with worse overall survival than NETs of the noncardia stomach independent of grade (p < 0.001). Poorly differentiated histology [hazard ratio (HR) 4.14, 95% confidence interval (CI) 2.26–7.57; p < 0.001] and distant metastases (HR 3.28, 95% CI 1.94–5.56; p < 0.001) were the greatest independent predictors of survival. For patients with poorly differentiated NETs, surgery was the only treatment to have benefit on overall survival (HR 0.38, 95% CI 0.27–0.54; p < 0.001) regardless of extent of disease. There was no additional benefit to adjuvant chemotherapy or radiation in patients undergoing resection (p = 0.39), even for patients with lymph node metastases (surgery alone versus surgery plus adjuvant therapy, p = 0.46), distant metastases (p = 0.19), or positive margins (p = 0.33).

Conclusions

Esophageal and gastric cardia NETs have worse survival than those of the noncardia stomach. Surgery offers the only survival benefit for poorly differentiated tumors, with no additional survival advantage to adjuvant chemotherapy or radiation.

https://ift.tt/2IGOh4n

Minimally Invasive Liver Surgery: Has it Achieved the Standard of Care?

https://ift.tt/2JyxFwD

Precision Hilar Cholangiocarcinoma Surgery

https://ift.tt/2IBApIr

Denis Parsons Burkitt, an Overlooked Surgical Oncologist

https://ift.tt/2JxnecT

Clinical Significance of Skeletal Muscle Loss Following Lung Resection for Cancer: Recovery and Sarcopenia are Linked to Cancer Outcomes

https://ift.tt/2IHlCMl

Significance of Glucose Transporter Type 1 (GLUT-1) Expression in the Therapeutic Strategy for Pancreatic Ductal Adenocarcinoma

Abstract

Background

This study aimed to examine the prognostic relevance of glucose transporter type 1 (GLUT-1), which is a key regulator of the glucose metabolism. In particular, the study aimed to examine the association between GLUT-1 expression and the therapeutic effect of chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC).

Methods

Patients with PDAC were enrolled in the study. Patients with distant metastases and those who received only chemotherapy as treatment were excluded from the study. Specimens for immunohistochemical evaluations were obtained through surgical resection and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the primary tumor before any treatment.

Results

This study included 197 patients. Of these 197 patients, 100 underwent upfront surgery, and 97 received neoadjuvant CRT (NACRT), which was performed mainly for patients with locally advanced tumors. Of the 97 patients who received NACRT, 21 later underwent surgical resection. For the patients who underwent upfront surgery, low GLUT-1 expression was an independent factor for a better prognosis. For the patients who underwent NACRT, low GLUT-1 expression was significantly associated with greater tumor size reduction, a higher resection rate, and a better prognosis. Additionally, GLUT-1 expression was significantly increased after NACRT treatment.

Conclusions

Among the patients with PDAC, those with low GLUT-1 expression in the primary tumor had a better prognosis those with high GLUT-1 expression. Moreover, the patients with low GLUT-1 expression displayed a better therapeutic response to NACRT.

https://ift.tt/2Jxn8Sz

Neural Invasion is a Significant Contributor to Peritoneal Recurrence in Signet Ring Cell Gastric Carcinoma

Abstract

Background

Gastric signet ring cell carcinoma (SRC) has shown a favorable outcome in early stages but has a worse prognosis than non-SRC in advanced stages. However, the cause for this stage-dependent prognostic impact has not been determined. This study aimed to compare clinicopathologic features and recurrence patterns between gastric SRC and non-SRC in a cohort of Eastern patients.

Methods

This study reviewed the prospectively collected data of 764 patients undergoing curative resection for gastric cancer from 2005 to 2008. The demographics, clinicopathologic characteristics, disease-specific survival (DSS) rate, and recurrence-free survival (RFS) rate of the patients were analyzed.

Results

The SRC patients (n = 176) had a worse prognosis than the non-SRC patients (n = 588), especially in stages T3 and T4. Peritoneal recurrence and the incidence of neural invasion (NI) were significantly increased in the SRC patients, albeit only in stages T3 and T4. In the T3 and T4 patients with NI, peritoneal recurrence occurred more frequently in SRC than in non-SRC (28.7% vs. 13.7%; p = 0.001), but not in the T3 and T4 patients without NI. Only in the patients with NI, SRC led to a significantly shorter DSS (67.6 vs. 90.7 months; p = 0.008) and RFS (67.1 vs. 80.3 months; p = 0.036) than non-SRC.

Conclusions

This report is the first to present the relationship between NI and peritoneal recurrence as the cause of stage-dependent prognoses for SRC. A better understanding of NI may lend insight into cancer spread and recurrence, especially in gastric SRC.

https://ift.tt/2EyzK82

The Negative Impact of Body Mass Index on the Tumor Microenvironment in Colon Cancer: Results of a Prospective Trial

Abstract

Background

The association between tumor mismatch repair status and obesity in colon cancer is not well understood. The authors of this study hypothesized that mismatch repair deficiency in colon cancer may be associated with a lower Body Mass Index (BMI) and improved patient outcome due to an enhanced tumor immune microenvironment.

Methods

For this study, 70 patients were randomly selected from a prospective trial evaluating nodal ultrastaging for colon cancer. The mismatch repair status of tumors and immunomarker expression were correlated with clinicopathologic characteristics and evaluated for disease-free survival.

Results

Patients with mismatch repair-deficient tumors (n = 11) had a lower mean BMI than those with mismatch repair-proficient tumors (n = 59) (22.16 vs. 26.30 kg/m², respectively; p = 0.029).The findings showed that CD3⁺ T cells were inversely associated with mismatch repair proficiency (p = 0.048). Mismatch repair-proficient tumors in nonobese patients (BMI < 30 kg/m²) versus obese patients had a higher density of CD8⁺ (p = 0.008) and FOXP3⁺ (p = 0.005) T cells. Multivariable analysis linked CD4⁺ (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.35–0.76), CD8⁺ (HR 0.67; 95% CI 0.50–0.89), and number of tumor-positive lymph nodes (HR 1.19; 95% CI 1.03–1.36) to disease-free survival for patients with mismatch repair-proficient tumors.

Conclusions

Tumor mismatch repair status and obesity are correlated in patients with colon cancer. Increased intratumoral T cells in nonobese patients suggests an unexplored link between tumor mismatch repair and immunoprofile.

https://ift.tt/2JyxjGj

A Population-based Study on Lymph Node Retrieval in Patients with Esophageal Cancer: Results from the Dutch Upper Gastrointestinal Cancer Audit

Abstract

Background

For esophageal cancer, the number of retrieved lymph nodes (LNs) is often used as a quality indicator. The aim of this study is to analyze the number of retrieved LNs in The Netherlands, assess factors associated with LN yield, and explore the association with short-term outcomes. This is a population-based study on lymph node retrieval in patients with esophageal cancer, presenting results from the Dutch Upper Gastrointestinal Cancer Audit.

Study Design

For this retrospective national cohort study, patients with esophageal carcinoma who underwent esophagectomy between 2011 and 2016 were included. The primary outcome was the number of retrieved LNs. Univariable and multivariable regression analyses were used to test for association with ≥ 15 LNs.

Patients and Results

3970 patients were included. Between 2011 and 2016, the median number of LNs increased from 15 to 20. Factors independently associated with ≥ 15 LNs were: 0–10 kg preoperative weight loss (versus: unknown weight loss, odds ratio [95% confidence interval]: 0.71 [0.57–0.88]), Charlson score 0 (versus: Charlson score 2: 0.76 [0.63–0.92]), cN2 category (reference: cN0, 1.32 [1.05–1.65]), no neoadjuvant therapy and neoadjuvant chemotherapy (reference: neoadjuvant chemoradiotherapy, 1.73 [1.29–2.32] and 2.15 [1.54–3.01]), minimally invasive transthoracic (reference: open transthoracic, 1.46 [1.15–1.85]), open transthoracic (versus open and minimally invasive transhiatal, 0.29 [0.23–0.36] and 0.43 [0.32–0.59]), hospital volume of 26–50 or > 50 resections/year (reference: 0–25, 1.94 [1.55–2.42] and 3.01 [2.36–3.83]), and year of surgery [reference: 2011, odds ratios (ORs) 1.48, 1.53, 2.28, 2.44, 2.54]. There was no association of ≥ 15 LNs with short-term outcomes.

Conclusions

The number of LNs retrieved increased between 2011 and 2016. Weight loss, Charlson score, cN category, neoadjuvant therapy, surgical approach, year of resection, and hospital volume were all associated with increased LN yield. Retrieval of ≥ 15 LNs was not associated with increased postoperative morbidity/mortality.

https://ift.tt/2IGqb9w

A Predictive Model for Axillary Node Pathologic Complete Response after Neoadjuvant Chemotherapy for Breast Cancer

Abstract

Background

Recent trials have suggested the feasibility of performing a sentinel lymph node biopsy (SNB) following neoadjuvant chemotherapy (NAC). The selection of suitable patients for this approach remains controversial. We developed a predictive model to identify patients most likely to benefit from SNB following NAC.

Methods

The National Cancer Data Base was used to identify patients with clinically node positive (cN+) breast cancer undergoing NAC followed by breast surgery and axillary lymph node dissection (ALND). Patients were randomly assigned to a 70% testing or 30% validation cohort for model development. A predictive model was built based on significant factors associated with pathologic nodal response (pN0) and breast response.

Results

Using the testing cohort (n = 13,396), multivariate regression was used to identify predictors of pN0 based on preoperative factors. Younger age, hormone receptor (HR)-negative/Her2-negative, HR-positive/Her2-positive, HR-negative/Her2-positive, high-grade, ductal histology, cN1 versus cN2, and extent of breast response were all significant independent predictors of pN0 on adjusted analysis. The odds ratios translated into a 10-point scale correlating to a stepwise increase in pN0 response. The area under the curve for the ROC curves for the testing and validation cohorts was 0.781 and 0.788, respectively (p < 0.01).

Conclusions

Our model incorporates known preoperative factors to predict the likelihood of pN0 response in patients with cN+ disease who undergo NAC. For patients with high scores, SNB should be considered over ALND, because these patients have a greater likelihood of having negative nodes at final pathology.

https://ift.tt/2JxmULd

Cervicothoracoscopic Approach for Esophageal Cancer in a Patient with Right-Sided Aortic Arch

Abstract

Background

Esophageal cancer frequently metastasizes to lymph nodes along the recurrent laryngeal nerve (RLN),1 therefore it is essential to dissect RLN nodes for curative esophagectomy.2 Right-sided aortic arch (RAA), a rare congenital anomaly, occurs in approximately 0.1% of adults.3 Because RAA forms a vascular ring encircling both the esophagus and the trachea at the cervicothoracic junction, its surgical anatomy is difficult to understand; hence, thoracoscopic dissection of RLN nodes is technically challenging. In this video, we applied the cervicothoracoscopic approach in a patient with esophageal squamous cell carcinoma and RAA, wherein the cervical operation was performed prior to the thoracoscopic operation.4

Methods

A 60-year-old woman was diagnosed with stage IA esophageal squamous cell carcinoma. During preoperative evaluation, we found that she had RAA with an aberrant left subclavian artery, and therefore decided to perform esophagectomy using the cervicothoracoscopic approach. In the cervical operation, we identified the RLN and dissected the lymph node in the cervicothoracic junction. The thoracoscopic operation was then performed from the left side with the patient in the prone position.

Results

The operation was successful. Total operative time was 548 min, with an estimated blood loss of 220 ml. There were no intraoperative and postoperative complications, and RLN palsy did not occur.

Conclusions

The vascular ring at the cervicothoracic junction in a patient with RAA made it difficult to dissect the RLN lymph nodes during oncologic esophagectomy. The cervicothoracoscopic approach enables the complete dissection of these lymph nodes and is a useful esophagectomy technique for patients with RAA.

https://ift.tt/2IEDBTv

Cytoplasmic Hu-Antigen R (HuR) Expression is Associated with Poor Survival in Patients with Surgically Resected Cholangiocarcinoma Treated with Adjuvant Gemcitabine-Based Chemotherapy

Abstract

Background

Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs).

Objective

The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection.

Methods

Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis.

Results

High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p < 0.01), while high cytoplasmic HuR expression was significantly associated with poor disease-free survival [DFS] (p = 0.03) and overall survival [OS] (p = 0.001) in the 91 patients who received AGC, but not in the 40 patients who did not receive AGC (DFS p = 0.17; OS p = 0.07). In the multivariate analysis of patients who received AGC, high cytoplasmic HuR expression was an independent predictor of poor DFS (hazard ratio [HR] 1.77; p = 0.04) and OS (HR 2.09; p = 0.02). Nuclear HuR expression did not affect the survival of enrolled patients.

Conclusions

High cytoplasmic HuR expression was closely associated with the efficacy of AGC in patients with cholangiocarcinoma. The current findings warrant further investigations to optimize adjuvant chemotherapy regimens for resectable cholangiocarcinoma.

https://ift.tt/2JxmIvt

Racial and Socioeconomic Differences in the Use of High-Volume Commission on Cancer-Accredited Hospitals for Cancer Surgery in the United States

Abstract

Background

Although major cancer surgery at a high-volume hospital is associated with lower postoperative mortality, the use of such hospitals may not be equally distributed.

Objective

Our aim was to study socioeconomic and racial differences in cancer surgery at Commission on Cancer (CoC)-accredited high-volume hospitals.

Methods

The National Cancer Database (NCDB) was used to identify patients undergoing surgery for colon, esophageal, liver, and pancreatic cancer from 2003 to 2012. Annual hospital volume for each cancer was categorized using quartiles of patient volume. Patient-level predictors of surgery at a high-volume hospital, trends in the use of a high-volume hospital, and adjusted likelihood of surgery at a high-volume hospital in 2012 versus 2003 were analyzed.

Results

African American patients were less likely to undergo surgery at a high-volume hospital for esophageal (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.49–0.73) and pancreatic cancer (OR 0.83, 95% CI 0.74–0.92), while uninsured patients and those residing in low educational attainment zip codes were less likely to undergo surgery at a high-volume hospital for esophageal, liver, and pancreatic cancer. In 2012, African Americans, uninsured patients, and those from low educational attainment zip codes were no more likely to undergo surgery at a high-volume hospital than in 2003 for any cancer type. These differences were not seen in colon cancer patients, for whom significant regionalization was not seen.

Conclusions

Differences in the use of CoC-accredited high-volume hospitals for major cancer surgery were seen nationwide and persisted over the duration of the study. Strategies to increase referrals and/or access to high-volume hospitals for African American and socioeconomically disadvantaged patients should be explored.

https://ift.tt/2ExVOjl

Essure Permanent Birth Control System by Bayer Healthcare: Announcement - FDA Restricts the Sale and Distribution

Audience: OBGYN, Patient, Risk Manager [Posted 04/09/2018] ISSUE: The FDA is aware that some women have received the Essure device without being adequately informed of Essure's risks. In order for this device to meet reasonable assurance of...

https://ift.tt/2JxGrv5

Laminar Flow-based Assays to Investigate Leukocyte Recruitment on Cultured Vascular Cells and Adherent Platelets

Leukocytes avidly interact with vascular cells and platelets after vessel wall injury or during inflammation. Here, we describe a straightforward laminar flow-based assay to characterize the molecular mechanisms that underlie the interactions between leukocytes and their cellular partners.

https://ift.tt/2GNeopA

https://ift.tt/2JzkSKE

https://ift.tt/2IC1rzy

Imaging the operated colon using water-enema multidetector CT, with emphasis on surgical anastomoses

Abstract

Water-enema multidetector CT (WE-MDCT) provides a detailed multiplanar visualisation of mural, intra- and extraluminal abnormalities of the large bowel, relying on preliminary bowel cleansing, retrograde luminal distension, pharmacological hypotonisation and intravenous contrast enhancement. In patients with a history of colorectal surgery for either carcinoma or Crohn's disease (CD), WE-MDCT may also be performed via a colostomy, which allows depicting the anatomy and position of the residual large bowel and evaluates the calibre, length, mural and extraluminal features of luminal strictures. Therefore, WE-MDCT may prove useful as a complementary technique after incomplete or inconclusive colonoscopy to assess features and suspected abnormalities of the surgical anastomosis, particularly when endoscopic or surgical interventions are being planned. This pictorial essay presents the WE-MDCT technique and pitfalls, the expected appearances after different colic surgeries and the imaging features of benign anastomotic disorders (fibrotic stricture, kinking, inflammatory ulcer) and of locally recurrent tumours and CD.

Teaching points

• Water-enema multidetector CT (WE-MDCT) effectively visualises the operated colon

• Complementary to endoscopy, WE-MDCT may helpfully depict abnormalities of surgical anastomoses

• WE-MDCT allows assessment of strictures' features and abnormalities of the upstream bowel

• Technical pitfalls, normal postsurgical findings and benign anastomotic disorders are presented

• WE-MDCT allows detecting relapsing Crohn's disease, recurrent and metachronous tumours

https://ift.tt/2IFqYYm

Assessing Collagen and Elastin Pressure-dependent Microarchitectures in Live, Human Resistance Arteries by Label-free Fluorescence Microscopy

We describe simultaneous mechanical testing and 3D-imaging of the arterial wall of isolated, live human resistance arteries, and Fiji and Ilastik image analyses for the quantification of elastin and collagen spatial organization and volume densities. We discuss the use of these data in mathematical models of arterial wall mechanics.

https://ift.tt/2qi5vhC

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

A facile fluorescence assay is presented to evaluate the efficiency of amino-acyl-tRNA-synthetase/tRNA pairs incorporating non-canonical amino-acids (ncAAs) into proteins expressed in mammalian cells. The application of ncAAs to study G-protein coupled receptors (GPCRs) is described, including photo-crosslinking mapping of binding sites and bioorthogonal GPCR labeling on live cells.

https://ift.tt/2GLWLGA

Visualizing the Actin and Microtubule Cytoskeletons at the B-cell Immune Synapse Using Stimulated Emission Depletion (STED) Microscopy

We present a protocol for using STED microscopy to simultaneously image actin structures, microtubules, and microtubule plus-end binding proteins in B cells that have spread on coverslips coated with antibodies to the B-cell receptor, a model for the initial phase of immune synapse formation.

https://ift.tt/2qhVLUp

Program Supporting Parent-Child Reading Aloud Aids Development

MONDAY, April 9, 2018 -- The Video Interaction Project (VIP), a parent education program which promotes positive parenting through reading aloud and play, reduces hyperactivity at school entry, according to a study published online April 9 in...

https://ift.tt/2uYkKky

High Financial Burden for Families of Patients With ASCVD

MONDAY, April 9, 2018 -- About one in four low-income families with a member with atherosclerotic cardiovascular disease (ASCVD) experience a high financial burden, according to a study presented at the American Heart Association's Quality of Care...

https://ift.tt/2Hr18bv

Polypharmacy Linked to Poorer Cognitive, Physical Capability

MONDAY, April 9, 2018 -- Polypharmacy is associated with poorer cognitive and physical capability even after adjustment for disease burden, according to a study published online March 24 in the Journal of the American Geriatrics Society. Mark James...

https://ift.tt/2uYkIcq

White Matter Tracts Differ for Infants With Fragile X Syndrome

MONDAY, April 9, 2018 -- There are significant differences in the development of 12 fiber tracts between infants with fragile X syndrome (FXS) and controls, according to a study published online April 4 in JAMA Psychiatry. Meghan R. Swanson, Ph.D.,...

https://ift.tt/2HmrESZ

Most Patients Are Unaware of Drug Cancer Shortages

MONDAY, April 9, 2018 -- Most people in the United States are unaware of national cancer drug shortages, according to a study published online April 9 in Cancer. Zachary A.K. Frosch, M.D., from the Dana-Farber Cancer Institute in Boston, and...

https://ift.tt/2v0jAEX

Increased Risk of Unnatural Death in People With Epilepsy

MONDAY, April 9, 2018 -- The risk of unnatural death is increased among people with epilepsy, according to a study published online April 9 in JAMA Neurology. Hayley C. Gorton, Ph.D., from the University of Manchester in the United Kingdom, and...

https://ift.tt/2HqpSk4

Variation in Quality of ICD Advice on Patient Message Boards

MONDAY, April 9, 2018 -- The quality of advice provided on patient-facing internet message boards discussing implanted cardiac defibrillator (ICD) treatment varies, with about 25 percent of the advice considered inappropriate for most patients,...

https://ift.tt/2v0jywP

Juvéderm Voluma XC Feasible for Correcting Infraorbital Hollows

MONDAY, April 9, 2018 -- Juvéderm Voluma XC is feasible and seems safe for correcting infraorbital hollows, according to a study published online April 5 in JAMA Facial Plastic Surgery. Michael B. Hall, M.D., from the Buckingham Center for Facial...

https://ift.tt/2Hnellg

Adult Patients With Diabetes Go to Dentist Less Often

MONDAY, April 9, 2018 -- People with diabetes and prediabetes visit the dentist less often than people without diabetes, according to a study published online March 31 in the Journal of the American Dental Association. Huabin Luo, Ph.D., from East...

https://ift.tt/2uZsTFh

Adults More Inclined to Take Tea, Pill for Hypertension

MONDAY, April 9, 2018 -- People would be more inclined to take tea or a pill than to exercise for hypertension, according to a study presented at the American Heart Association's Quality of Care and Outcomes Research 2018 Scientific Sessions, held...

https://ift.tt/2Hnempk

https://ift.tt/2GQvF1i

Association of Expression Levels or Activation Status of STAT3 with Treatment Outcomes of Sunitinib in Patients with Renal Cell Carcinoma

Abstract

Background

The expression level of signal transducer and activator of transcription 3 (STAT3) in tumor cells is reported to associate with response to therapy and with survival time in various types of cancer.

Objective

This retrospective study aimed to elucidate the association of STAT3 expression in tumor cells with the therapeutic outcomes of sunitinib in patients with renal cell carcinoma (RCC).

Patients and Methods

Patients with metastatic RCC who received sunitinib therapy were enrolled in this study. All patients underwent nephrectomy for RCC, and nephrectomy specimens were stained for STAT3 and phosphorylated STAT3 (p-STAT3) by immunohistochemistry.

Results

We assessed 51 patients receiving sunitinib as a first-line therapy. STAT3 expression levels did not influence progression-free survival (PFS) and overall survival (OS); however, patients with p-STAT3-positive tumors exhibited significantly worse PFS compared with those with p-STAT3-negative tumors (log-rank test, P = 0.034). OS tended to be prolonged in patients with p-STAT3-negative tumors. Objective response rate or disease control rate based on the best overall response did not show a significant association with STAT3 or p-STAT3 expression. Univariate Cox proportional hazard regression analyses for clinical predictors revealed that p-STAT3 positivity significantly correlated with shorter PFS (hazard ratio [HR], 2.22, P = 0.041), whereas p-STAT3 expression was not related to the OS.

Conclusions

Activated STAT3 in tumor tissues shows a significant association with poor prognosis in patients with RCC who received sunitinib as a first-line therapy, and positive p-STAT3 expression could be a potential biomarker for refractoriness to sunitinib therapy.

https://ift.tt/2GOwZ4N

Production and Purification of Baculovirus for Gene Therapy Application

In this protocol, baculovirus is produced by transient transfection of baculovirus plasmid into Sf9 cells and amplified in a serum-free suspension culture. The supernatant is purified by heparin affinity chromatography and further concentrated by ultracentrifugation. This protocol is useful for the production and purification of baculovirus for gene therapy application.

https://ift.tt/2GJ1RHz

Synthesis of a Thiol Building Block for the Crystallization of a Semiconducting Gyroidal Metal-sulfur Framework

Here, we present a one-pot, transition-metal-free synthesis of thiols and thioesters from aromatic halides and sodium thiomethoxide, followed by the preparation of single crystals of a metal-dithiolene network using thiol species generated in situ from the more stable and tractable thioester.

https://ift.tt/2qlDXqH

General recommendations paper on the management of older patients with cancer: the SEOM geriatric oncology task force’s position statement

Abstract

Population aging is associated with greater numbers of older people with cancer. Thanks to treatment advances, not only are more seniors diagnosed with cancer, but there are also more and more older cancer survivors. This upward trend will continue. Given the heterogeneity of aging, managing older patients with cancer poses a significant challenge for Medical Oncology. In Spain, a Geriatric Oncology Task Force has been set up within the framework of the Spanish Society for Medical Oncology (SEOM). With the aim of generating evidence and raising awareness, as well as helping medical oncologists in their training with respect to seniors with cancer, we have put together a series of basic management recommendations for this population. Many of the patients who are assessed in routine clinical practice in Oncology are older. CGA is the basic tool by means of which to evaluate older people with cancer and to understand their needs. Training and the correct use of recommendations regarding treatment for comorbidities and geriatric syndromes, support care, and drug–drug interactions and toxicities, including those of antineoplastic agents, as detailed in this article, will ensure that this population is properly managed.

https://ift.tt/2Hm19NL

Evaluation of waiting times for breast cancer diagnosis and surgical treatment

Abstract

Purpose

To analyse any delays in breast cancer diagnosis and surgical treatment, influence of clinical and biological factors and influence of delays on survival.

Methods/patients

A descriptive, observational, and retrospective study was conducted between 2006 and 2016 on stages I–III breast cancer patients. This is a retrospective review of health records to collect data on delays, patients' clinical data, biological features of the tumour and information on treatment. Mortality data from the National Death Index.

Results

In 493 evaluable patients, the median of days from the first symptom to mammography, biopsy, and surgery was 41, 57, and 92, respectively. The median of days from screening mammography to biopsy and surgery was 10 and 51, respectively. From biopsy to surgery, the median was 34 days in every case. Over the last 5 years, an increase in biopsy–surgery delay has been observed (p = 0.0001). Tumour stages I and II vs. stage III (RR 1.74. 95% CI 1.08–2.80, p = 0.027), diagnosis in screening (RR 0.66. 95% CI 0.45–0.96, p = 0.030), and use of magnetic resonance imaging (RR 2.08. 95 CI 1.21–3.56, p = 0.008) condition a greater biopsy–surgery delay. No influence of delays on survival has been identified.

Conclusions

Delays in diagnosis and surgery in the case of women diagnosed on the basis of symptoms may be improved. There is a temporary tendency to a greater delay in surgery. Some clinical and biological factors must be taken into account to optimise delays. Survival results are not adversely affected by delays.

https://ift.tt/2v4byLE

Re-expression of microRNA-4319 inhibits growth of prostate cancer via Her-2 suppression

Abstract

Purpose

Her-2 is an epidermal growth factor receptor expressed in some prostate cancers (PC) associated with outgrowth of the tumor. Dysregulation of some microRNAs is involved in the regulation of PC pathogenesis, whereas the role of miR-4319 in PC is unknown and addressed in the current study.

Methods

The levels of miR-4319 in PC tissues were determined by RT-qPCR and their association with patient survival was studied by Kaplan–Meier analysis. Targeted genes for miR-4319 were predicted by a bioinformatics algorithm and confirmed by a dual-luciferase reporter assay. Growth of cells of overexpression or inhibition of miR-4319 or Her-2 was analyzed by an MTT assay. Cell survival in response to a chemotherapeutic drug, estramustine (EM), was analyzed by CCK-8 assay. Cell apoptosis was evaluated by TUNEL assay and Western blotting for apoptosis-associated proteins.

Results

MiR-4319 levels were decreased in PC specimens, compared to corresponding normal prostate tissue. Lower levels of miR-4319 were correlated with poorer overall patients' survival. In vitro, the cell survival mediated with Her-2 against chemotherapy was inhibited by overexpression of miR-4319 and was enhanced by depletion of miR-4319. Depletion of miR-4319 in primary prostate epithelial cells increased Her-2-dependent cell growth, while re-expression of miR-4319 in PC cells inhibited Her-2-dependent cell growth and Her-2-dependent resistance to EM-induced apoptosis.

Conclusion

The growth and chemo-resistance of PC cells may be suppressed via re-expression of miR-4319 that inhibits Her-2 signaling.

https://ift.tt/2Hm16S5

Cocaine and Beta Blockers – That Dogmalysis Won’t Hunt

by Jeff Lapoint     Everyone wins, if winning is being angry – Alexis C. Madrigal There was a Life in the Fast Lane post in 2016 that chronicled an intrepid clinician justifying beta blocker use in cocaine toxicity. It began with a clinical vignette involving a student who, in attempting to make it through a […]

EMCrit Project by Tox & Hound.

https://ift.tt/2Ju9qzM

LncRNA NEAT1/let-7a-5p axis regulates the cisplatin resistance in nasopharyngeal carcinoma by targeting Rsf-1 and modulating the Ras-MAPK pathway

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https://ift.tt/2qnIwSr

Efficacy of Endoscopic Management for Early Remnant Gastric Cancer: Is Completion Gastrectomy Truly Necessary in Cases with Marginally Noncurative Histopathologic Features?

Abstract

Background

For patients with early primary gastric cancer, endoscopic management has become a standard of care. However, its efficacy for early remnant gastric cancer (ERGC) remains controversial and an invasive surgical procedure remains the primary choice of treatment.

Methods

A multi-institutional database of ERGC cases was retrospectively reviewed. Efficacy of endoscopic resection was analyzed by reviewing the clinicopathologic features of patients who underwent endoscopic resection and comparing the long-term outcomes with those of surgical resection.

Results

Of the 121 patients who were histopathologically diagnosed with ERGC after distal gastrectomy, 80 underwent endoscopic resection and 41 underwent completion gastrectomy (Group S). According to the histopathological criteria, 55 of the 80 endoscopic resection cases were classified as "curative resection" (Group E1) and the remaining 25 were classified as "noncurative resection" (Group E2). Tumor recurrence was observed only in three patients (12%) in Group E2, and no tumor recurrence was confirmed in Group S and Group E1. Multivariate analyses confirmed that completion gastrectomy [hazard ratio (HR), 6.2; 95% confidence interval (CI), 1.5–26.3] was associated with poor survival compared with endoscopic resection, and lymphovascular infiltration (HR 9.5; 95% CI 2.5–36.7) was correlated with tumor recurrence. Histopathological positive resection margin, tumor size, or deeper tumor invasion were not correlated with tumor recurrence after endoscopic resection.

Conclusions

Endoscopic management might be an effective treatment option for ERGC with potential long-term survival advantage over the completion gastrectomy even in cases with histopathological features, suggesting noncurative resection.

https://ift.tt/2Ewyv9F