Social determinants of health and outcomes of ventral hernia repair in a safety-net hospital setting.

PURPOSE: Lower socioeconomic status has been shown to be predictive of poorer surgical outcomes in ventral hernia repair. Recently, safety-net hospitals have been attempting to address these disparities to improve the care of patients of lower socioeconomic status. METHODS: A query of all patients undergoing ventral hernia repair at our institution between 2010 and 2019 was completed (n = 580). Patients not from identifiable New Jersey ZIP-codes were excluded (n = 572). ZIP codes were assigned quartiles based off socioeconomic variables including median household income, percent below poverty line, and high school graduation rate. Patients were then assigned to socioeconomic status quartiles based off their residential ZIP-code. Outcomes of ventral hernia surgery were compared across ZIP-code quartiles. Logistic regression was used to analyze predictors of poor outcomes. RESULTS: Patients from lower socioeconomic brackets were more likely to be younger (p < 0.001), female (p = 0.014), black (p < 0.001), and/or Hispanic (p = 0.003). Most notably, outcomes of ventral hernia were not significantly different between patients of different socioeconomic status ZIP-code quartiles. The risk of any post-operative morbidity was higher for longer procedures (p < 0.001) and for hernia repairs being done with other procedures (p < 0.001). Risk of prolonged length of stay and related 30-day readmission was higher with longer procedures (p < 0.001 and p = 0.003, respectively). CONCLUSION: We found that outcomes of ventral hernia repair at a safety-net hospital were unaffected by socioeconomic status. This supports the important role that safety-net institutions play in providing quality care to their vulnerable populations. Future studies at other safety-net hospitals should be done to further assess the updated impact of socioeconomic status on ventral hernia outcomes.

Abdominal adiposity assessed using CT angiography associates with acute kidney injury after trans-catheter aortic valve replacement.

AIM: To determine if there is an association between area-based visceral abdominal adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAT), and abdominal circumference measured on computed tomography (CT) angiography before trans-catheter aortic valve replacement (TAVR) and post-TAVR acute kidney injury (AKI). MATERIALS AND METHODS: In this retrospective cohort study of 106 TAVR patients, SAT and VAT areas and abdominal circumference was measured on a single CT section at L4 vertebral level. Univariate comparisons between patients who did and did not develop AKI were undertaken for radiological measurements. Multivariable logistic regression was used to assess association between CT measurements and the development of post-TAVR AKI. RESULTS: Post-TAVR AKI occurred in 20 of 106 patients (19%). In univariate comparisons, body mass index (BMI) did not differ significantly between patients who did and did not develop AKI (p=0.14); however, VAT+SAT (443.2±163.7 versus 351±168.7 cm2; p=0.03), VAT (213.9±110.6 versus 153.9±96.1 cm2; p=0.03), and outer abdominal circumference (100.2±14.4 cm versus 91.8±13.3 cm; p=0.02) were significantly higher in the patients who did not develop post-TAVR AKI. These three measures on pre-TAVR CT angiogram remained significantly associated with reduced post-TAVR AKI with a lower incidence of post-TAVR AKI after multivariable adjustment for pre-TAVR estimated glomerular filtration rate and patient height (p<0.05). CONCLUSION: This study found that increased abdominal obesity as assessed by measures on pre-TAVR CT angiogram is associated with a significantly lower incidence of AKI.

The effect of smoking on surgical outcomes in ventral hernia repair: a propensity score matched analysis of the National Surgical Quality Improvement Program data.

PURPOSE: Although studies have implicated smoking as a positive predictor of post-operative outcomes in inguinal hernia repair, its impact on ventral hernia repair (VHR) is not as clear. This study aims to fill this gap by investigating the impact of smoking on developing adverse 30-day post-operative outcomes in VHR. METHODS: Patients undergoing VHR between 2005 and 2014 were extracted from the American College of Surgeons National Surgical Quality Improvement Program database. Patients were stratified by smoking status and compared for significant differences in baseline characteristics. Logistic regression modeled the impact of smoking on the primary outcome variable of 30-day mortality and the secondary outcome variables of 30-day overall, cardiac, respiratory, or wound morbidity. To evaluate the influence of smoking in comparable groups undergoing VHR, a propensity score matched analysis was performed. RESULTS: Out of 169,458 patients identified, 32,973 (19.5%) were classified as current smokers. Smokers and non/ex-smokers differed significantly in multiple pre-operative baseline characteristics. Unmatched univariate analyses revealed smoking status as a positive predictor of every post-operative outcome. These findings were validated with propensity score matching analyses, which found current smokers have an increased likelihood of 30-day mortality (OR 1.42), overall morbidity (OR 1.39), wound (OR 1.40), respiratory (OR 1.14), or cardiac morbidity (OR 1.88) compared to non/ex-smokers (p < 0.05 for all). CONCLUSIONS: Smoking is a modifiable risk factor with a detrimental impact on outcomes in patients undergoing ventral hernia repair. Delaying VHR and promoting smoking cessation prior to surgery may help reduce the odds of adverse 30-day post-operative outcomes.

Incarcerated inguinal hernia and small bowel obstruction as a rare complication of a penile prosthesis.

In this paper, we present a rare case of a small bowel obstruction secondary to an incarcerated inguinal hernia as a short-term complication of a penile prosthesis implantation. The patient underwent prosthesis implantation to treat refractory erectile dysfunction after a robotic-assisted laparoscopic radical prostatectomy. He presented 2 weeks later with the incarcerated hernia to our emergency department and surgical service. The hernia was repaired in a tension-free manner, and the bowel was uncompromised. The patient is symptom free at follow-up.

Study of the decay B0(B- 0)-->rho+rho-, and constraints on the Cabibbo-Kobayashi-Maskawa angle alpha.

Using a data sample of 89 x 10(6) Upsilon(4S)-->BB decays collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC, we measure the B0(B (0))-->rho(+)rho(-) branching fraction as [30+/-4(stat)+/-5(syst)]x10(-6) and a longitudinal polarization fraction of f(L)=0.99+/-0.03(stat)+0.04-0.03(syst). We measure the time-dependent-asymmetry parameters of the longitudinally polarized component of this decay as C(L)=-0.17+/-0.27(stat)+/-0.14(syst) and S(L)=-0.42+/-0.42(stat)+/-0.14(syst). We exclude values of alpha between 19 degrees and 71 degrees (90% C.L.).

Measurements of CP-violating asymmetries in B0-->K(0)(s)pi(0) decays.

We present a measurement of the time-dependent CP-violating (CPV) asymmetries in B0-->K(0)(S)pi(0) decays based on 124x10(6) Upsilon(4S)-->BB decays collected with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. In a sample containing 122+/-16 signal decays, we obtain the magnitudes of the direct CPV asymmetry CK(0)(S)(pi(0))=0.40(+0.27)(-0.28)+/-0.09 and of the CPV asymmetry in the interference between mixing and decay SK(0)(S)(pi(0))=0.48(+0.38)(-0.47)+/-0.06 where the first error is statistical and the second systematic.

Search for B+/--->[K(-/+)pi(+/-)](D)K+/- and upper limit on the b-->u amplitude in B+/--->DK+/-.

We search for B+/--->[K(-/+)pi(+/-)](D)K+/- decays, where [K(-/+)pi(+/-)](D) indicates that the K-/+pi(+/-) pair originates from the decay of a D0 or D (0). Results are based on 120x10(6) Upsilon(4S)-->BB decays collected with the BABAR detector at SLAC. We set an upper limit on the ratio R(Kpi) identical with[Gamma(B+-->[K(-)pi(+)](D)K+)+Gamma(B--->[K(+)pi(-)](D)K-)][Gamma(B+-->[K(+)pi(-)](D) / K+)+Gamma(B--->[K(-)pi(+)](D)K-)]<0.026 (90% C.L.). This constrains the amplitude ratio r(B) identical with|A(B--->D 0K-)/A(B--->D0K-)|<0.22 (90% C.L.), consistent with expectations. The small value of r(B) favored by our analysis suggests that the determination of the Cabibbo-Kobayashi-Maskawa phase gamma from B-->DK will be difficult.

Measurement of the B-->Xsl+l- branching fraction with a sum over exclusive modes.

We measure the branching fraction for the flavor-changing neutral-current process B-->X(s)l(+)l(-) with a sample of 89x10(6) Upsilon(4S)-->BBmacr; events recorded with the BABAR detector at the PEP-II e(+)e(-) storage ring. The final state is reconstructed from e(+)e(-) or micro(+)micro(-) pairs and a hadronic system X(s) consisting of one K+/- or K(0)(S) and up to two pions, with at most one pi(0). We observe a signal of 40+/-10(stat)+/-2(syst) events and extract the inclusive branching fraction B(B-->X(s)l(+)l(-))=(5.6+/-1.5(stat)+/-0.6(exp syst)+/-1.1(model syst))x10(-6) for ml(+)(l(-))>0.2 GeV/c(2).

Measurement of the direct CP asymmetry in b-->s gamma Decays.

We describe a measurement of the direct CP asymmetry between inclusive b-->s gamma and b-->s gamma decays. This asymmetry is expected to be less than 0.01 in the standard model, but could be enhanced up to about 0.10 by new physics contributions. We use a sample of 89 x 10(6) BB pairs recorded with the BABAR detector at SLAC PEP-II, from which we reconstruct a set of 12 exclusive b-->s gamma final states containing one charged or neutral kaon and one to three pions. We measure an asymmetry of A(CP)(b-->s gamma)=0.025+/-0.050(stat)+/-0.015(syst), corresponding to an allowed range of -0.06s gamma)<+0.11 at 90% confidence level.

Measurement of the time-dependent CP asymmetry in the B0-->phiK0 decay.

We present a measurement of the time-dependent CP asymmetry for the neutral B-meson decay B0-->phiK0. We use a sample of approximately 114 x 10(6) B-meson pairs taken at the Upsilon(4S) resonance with the BABAR detector at the PEP-II B-meson factory at SLAC. We reconstruct the CP eigenstates phiK0S and phiK0L, where phi-->K+K-, K0S-->pi+pi-, and K0L is observed via its hadronic interactions. The other B meson in the event is tagged as either a B0 or Bbar0 from its decay products. The values of the CP-violation parameters are SphiK=0.47+/-0.34(stat)+0.08-0.06(syst) and CphiK=0.01+/-0.33(stat)+/-0.10(syst).

An efficient route to human bispecific IgG.

Production of bispecific IgG (BsIgG) by coexpressing two different antibodies is inefficient due to unwanted pairings of the component heavy and light chains. To overcome this problem, heavy chains were remodeled for heterodimerization using engineered disulfide bonds in combination with previously identified "knobs-into-holes" mutations. One of the variants, S354C:T366W/Y349'C:T366'S:L368'A:Y407++ +'V, gave near quantitative (approximately 95%) heterodimerization. Light chain mispairing was circumvented by using an identical light chain for each arm of the BsIgG. Antibodies with identical light chains that bind to different antigens were identified from an scFv phage library with a very restricted light chain repertoire for the majority (50/55) of antigen pairs tested. A BsIgG capable of simultaneously binding to the human receptors HER3 and cMpI was prepared by coexpressing the common light chain and corresponding remodeled heavy chains followed by protein A chromatography. The engineered heavy chains retain their ability to support antibody-dependent cell-mediated cytotoxicity as demonstrated with an anti-HER2 antibody.

Engineering antibodies for imaging and therapy.

Several advances made during the past year will probably facilitate the development of therapeutic antibodies. Most notably, significant progress has been made in the rapid isolation of high affinity human antibodies from phage display libraries and by immunization of transgenic mice. The therapeutic potential of bispecific antibody fragments and Fc-containing proteins has been greatly enhanced by improved production methods. The utility of radiolabeled antibody fragments has been improved by the development of site-specific labeling methods and by the advent of the 'minibody', an engineered fragment that has proved to be highly successful for tumor imaging in mice.

A lesion in the DNA replication initiation factor Mcm10 induces pausing of elongation forks through chromosomal replication origins in Saccharomyces cerevisiae.

We describe a new minichromosome maintenance factor, Mcm10, and show that this essential protein is involved in the initiation of DNA replication in Saccharomyces cerevisiae. The mcm10 mutant has an autonomously replicating sequence-specific minichromosome maintenance defect and arrests at the nonpermissive temperature with dumbbell morphology and 2C DNA content. Mcm10 is a nuclear protein that physically interacts with several members of the MCM2-7 family of DNA replication initiation factors. Cloning and sequencing of the MCM10 gene show that it is identical to DNA43, a gene identified independently for its putative role in replicating DNA. Two-dimensional DNA gel analysis reveals that the mcm10-1 lesion causes a dramatic reduction in DNA replication initiation at chromosomal origins, including ORI1 and ORI121. Interestingly, the mcm10-1 lesion also causes replication forks to pause during elongation through these same loci. This novel phenotype suggests a unique role for the Mcm10 protein in the initiation of DNA synthesis at replication origins.

Cell cycle-regulated nuclear localization of MCM2 and MCM3, which are required for the initiation of DNA synthesis at chromosomal replication origins in yeast.

MCM2 and MCM3 are two genetically interacting and structurally related proteins essential for growth in Saccharomyces cerevisiae. Mutants defective in these proteins affect the stability of minichromosomes in general, but the severity of the defect is dependent on the autonomously replicating sequence (ARS) that drives the replication of that plasmid. In this paper we show by two-dimensional gel electrophoresis that the initiation of DNA synthesis at chromosomal replication origins is also reduced in frequency in these mutants. We show further that the nuclear and subnuclear localizations of the MCM2 and MCM3 proteins are temporally regulated with respect to the cell cycle. These proteins enter the nucleus at the end of mitosis, persist there throughout G1 phase, and disappear from it at the beginning of S phase. Once inside the nucleus, a fraction of the MCM2 and MCM3 proteins becomes tightly associated with DNA. The association of MCM2 and MCM3 with chromatin presumably leads to the initiation of DNA synthesis, and their subsequent disappearance from the nucleus presumably prevents reinitiation of DNA synthesis at replication origins. This temporally and spatially restricted localization of MCM2 and MCM3 in the nucleus may serve to ensure that DNA replication occurs once and only once per cell cycle.