Milk oligosaccharides are associated with improved health outcomes in infants. Nanofiltration (NF) is used for isolation of bovine milk oligosaccharides (BMO). The study aim was to improve the recovery of BMO from lactose-hydrolyzed colostrum whey permeate. The retention factors of carbohydrates at various pH and transmembrane pressures were determined for a nanofiltration membrane, which was used at pilot scale to purify BMO. Carbohydrates were quantified by liquid chromatography and characterized using nano-LC-Chip-QToF mass spectrometry. BMO purity was improved from an initial 4% in colostrum whey permeate to 98%, with 99.8% permeation of monosaccharides and 96% recovery of oligosaccharides, represented by 23 unique BMO compounds identified in the final retentate. The pH during NF was a determining factor in the selectivity of carbohydrate separation. This NF method can be applied to conventional cheese-whey permeate and other milk types for extraction of bioactive oligosaccharides providing new options for the dairy industry.

The vertical rectus abdominis myocutaneous (VRAM) flap is a versatile and well-established reconstructive technique for many defects created as a result of colorectal and gynecologic extirpation. However, major re-operation in the pelvis following a VRAM flap reconstruction several months later is uncommon, and the safety and integrity of the VRAM flap in this setting has not been described. This case examines VRAM flap preservation during repeat exploratory laparotomy, and a unique view of the VRAM flap during interval exploration. We demonstrate an intact flap after lysis of adhesions with an audible Doppler signal, and maintenance of flap integrity in the postoperative period. This further substantiates its use as a durable rotational flap for perineal tissue defects.

Objective

Frailty has been associated with poorer surgical outcomes and is a critical factor in procedural risk assessment. The objective of this study is to assess the impact of frailty on surgical outcomes in patients with endometrial cancer.

Methods

Patients undergoing inpatient gynecologic surgery for endometrial cancer were identified using the 2005-2017 Nationwide Inpatient Sample database. The Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator was used to designate frailty. Multivariate regression models were used to assess the association of frailty with postoperative outcomes and resource use.

Results

Of 339 846 patients, 2.9% (9868) were considered frail. After adjusting for patient and hospital characteristics, frailty was associated with a four-fold increase in inpatient mortality (adjusted OR (aOR) 4.1; p<0.001), non-home discharge (aOR 5.2; p<0.001), as well as increased respiratory (aOR 2.6; p<0.001), neurologic (aOR 3.3; p<0.001), renal (aOR 2.0; p<0.001), and infectious (aOR 3.2; p<0.001) complications. While frail patients exhibited increased mortality with age, the rate of mortality in this cohort decreased significantly over time. Compared with non-frail counterparts, frail patients had longer lengths of stay (7.6 vs 3.4 days; p<0.001) and increased hospitalization costs with surgical admission ($25 093 vs $13 405; p<0.001).

Conclusions

Frailty is independently associated with worse surgical outcomes, including increased mortality and resource use, in women undergoing surgery for endometrial cancer. Though in recent years there have been improvements in mortality in the frail population, further efforts to mitigate the impact of frailty should be explored.

As more is learned about glycoproteins' roles in human health and disease, the biological functionalities of N-linked glycans are becoming more relevant. Protein deglycosylation allows for the selective release of N-glycans and facilitates glycoproteomic investigation into their roles as prebiotics or anti-pathogenic factors. To increase throughput and enzyme reusability, this work evaluated several immobilization methods for an endo-β-N-acetylglucosaminidase recently discovered from the commensal Bifidobacterium infantis. Ribonuclease B was used as a model glycoprotein to compare N-glycans released by the free and immobilized enzyme. Amino-based covalent method showed the highest enzyme immobilization. Relative abundance of N-glycans and enzyme activity were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Kinetic evaluation demonstrated that upon immobilization, both V_max and the K_m decreased. Optimal pH values of 5 and 7 were identified for the free and immobilized enzyme, respectively. Although a higher temperature (65 vs. 45 °C) favored rapid glycan release, the immobilized enzyme retained over 50% of its original activity after seven use cycles at 45 °C. In view of future applications in the dairy industry, we investigated the ability of this enzyme to deglycosylate whey proteins. The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.

Glycans play important biological roles in cell-to-cell interactions, protection against pathogens, as well as in proper protein folding and stability, and are thus interesting targets for scientists. Although their mechanisms of action have been widely investigated and hypothesized, their biological functions are not well understood due to the lack of deglycosylation methods for large-scale isolation of these compounds. Isolation of glycans in their native state is crucial for the investigation of their biological functions. However, current enzymatic and chemical deglycosylation techniques require harsh pretreatment and reaction conditions (high temperature and use of detergents) that hinder the isolation of native glycan structures. Indeed, the recent isolation of new endoglycosidases that are able to cleave a wider variety of linkages and efficiently hydrolyze native proteins has opened up the opportunity to elucidate the biological roles of a higher variety of glycans in their native state. As an example, our research group recently isolated a novel Endo-β-N-acetylglucosaminidase from Bifidobacterium longum subsp. infantis ATCC 15697 (EndoBI-1) that cleaves N-N'-diacetyl chitobiose moieties found in the N-linked glycan (N-glycan) core of high mannose, hybrid, and complex N-glycans. This enzyme is also active on native proteins, which enables native glycan isolation, a key advantage when evaluating their biological activities. Efficient, stable, and economically viable enzymatic release of N-glycans requires the selection of appropriate immobilization strategies. In this review, we discuss the state-of-the-art of various immobilization techniques (physical adsorption, covalent binding, aggregation, and entrapment) for glycosidases, as well as their potential substrates and matrices. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:104-112, 2017.

Objective

To characterize factors associated with high-cost inpatient admissions for ovarian cancer.

Methods

Operative hospitalizations for ovarian cancer patients ≥65 years of age were identified using the 2010-2017 National Inpatient Sample. Admissions with high-cost were defined as those incurring ≥90th percentile of hospitalization costs each year, while the remainder were considered low-cost. Multivariable logistic regression models were developed to assess independent predictors of being in the high-cost cohort.

Results

During the study period, an estimated 58,454 patients met inclusion criteria. 5827 patient admissions (9.98%) were classified as high-cost. Median hospitalization cost for this high-cost group was $55,447 (interquartile range (IQR) $46,744-$74,015) compared to $16,464 (IQR $11,845-$23,286, p < 0.001) for the low-cost group. Patients with high-cost admissions were more likely to have received open (adjusted odds ratio (AOR) 2.23, 1.31-3.79) or extended (AOR 5.64, 4.79-6.66) procedures and be admitted non-electively (AOR 3.32, 2.74-4.02). Being in the top income quartile (AOR 1.77, 1.39-2.27) was also associated with high-cost. Age and hospital factors, including bed size and volume of gynecologic oncology surgery, did not affect cost group.

Conclusion

High-cost ovarian cancer admissions were three times more expensive than low-cost admissions. Fewer open and extended procedures with subsequently shorter lengths of stay may have contributed to decreasing inpatient costs over the study period. In this cohort of patients largely covered by Medicare, clinical factors outweigh socioeconomic factors as cost drivers. Understanding the relationship of disease-specific and social factors to cost will be important in informing future value-based quality improvement efforts in gynecologic cancer care.

OBJECTIVE: We aimed to identify social needs of gynecologic oncology patients using a self-administered social needs assessment tool (SNAT), compare the SNAT to a formal social work assessment performed by cancer care navigators (CCN), and provide SNAT-informed community resources. METHODS: We analyzed prospectively collected data from a performance improvement initiative in a safety-net gynecologic oncology clinic between October 2021 and July 2022. We screened for eight social needs domains, health literacy, desire for social work, and presence of urgent needs. Clinicodemographic data were abstracted from the electronic medical record. Univariate descriptive statistics were used. Inter-rater reliability for social needs domains was assessed using percent agreement. RESULTS: 1010 unique patients were seen over this study period. 488 (48%) patients completed the SNAT, of which 265 (54%) screened positive for ≥1 social need. 83 (31%) patients were actively receiving cancer treatment, 140 (53%) were in post-treatment surveillance, and 42 (16%) had benign gynecologic diagnoses. Transportation (19% vs 25%), housing insecurity (18% vs 19%), and desire to speak with a social worker (16% vs 27%) were the 3 most common needs in both the entire cohort and among patients actively receiving cancer treatment. 78% patients in active treatment were seen by a CCN and received SNAT informed community resources. The percent agreement between the SNAT and formal CCN assessment ranged from 72%-94%. CONCLUSIONS: The self-administered SNAT identified many unmet social needs among gynecologic oncology patients, corresponded well with the formal social work CCN assessment, and informed the provision of community resources.

BACKGROUND: The rise of depression, anxiety, and suicide rates has led to increased demand for telemedicine-based mental health screening and remote patient monitoring (RPM) solutions to alleviate the burden on, and enhance the efficiency of, mental health practitioners. Multimodal dialog systems (MDS) that conduct on-demand, structured interviews offer a scalable and cost-effective solution to address this need. OBJECTIVE: This study evaluates the feasibility of a cloud based MDS agent, Tina, for mental state characterization in participants with depression, anxiety, and suicide risk. METHOD: Sixty-eight participants were recruited through an online health registry and completed 73 sessions, with 15 (20.6%), 21 (28.8%), and 26 (35.6%) sessions screening positive for depression, anxiety, and suicide risk, respectively using conventional screening instruments. Participants then interacted with Tina as they completed a structured interview designed to elicit calibrated, open-ended responses regarding the participants feelings and emotional state. Simultaneously, the platform streamed their speech and video recordings in real-time to a HIPAA-compliant cloud server, to compute speech, language, and facial movement-based biomarkers. After their sessions, participants completed user experience surveys. Machine learning models were developed using extracted features and evaluated with the area under the receiver operating characteristic curve (AUC). RESULTS: For both depression and suicide risk, affected individuals tended to have a higher percent pause time, while those positive for anxiety showed reduced lip movement relative to healthy controls. In terms of single-modality classification models, speech features performed best for depression (AUC = 0.64; 95% CI = 0.51-0.78), facial features for anxiety (AUC = 0.57; 95% CI = 0.43-0.71), and text features for suicide risk (AUC = 0.65; 95% CI = 0.52-0.78). Best overall performance was achieved by decision fusion of all models in identifying suicide risk (AUC = 0.76; 95% CI = 0.65-0.87). Participants reported the experience comfortable and shared their feelings. CONCLUSION: MDS is a feasible, useful, effective, and interpretable solution for RPM in real-world clinical depression, anxiety, and suicidal populations. Facial information is more informative for anxiety classification, while speech and language are more discriminative of depression and suicidality markers. In general, combining speech, language, and facial information improved model performance on all classification tasks.

Background

Methamphetamine (MA) use increased during COVID-19, with men who have sex with men (MSM) exhibiting 3-fold greater use than heterosexual men. Understanding links between reported MA use and COVID-19 prevention behaviors among MSM can inform current transmission risks for HIV, Monkeypox, and other infectious diseases.

Methods

This study assesses relationships between self-reported pattern of MA use (past six months; past two weeks) and reported COVID-19 preventive behaviors, adjusting for participant characteristics (HIV serostatus, race/ethnicity, employment and housing stability), in a cohort of ethnically diverse MSM in Los Angeles, California, between April 1 and September 30, 2020.

Results

Compared to those who reported no MA use, MSM who reported weekly or more MA use in the past six months were significantly less likely to use COVID-19 protective behaviors of physical distancing (61.8% vs. 81.6%; AOR = 0.39, 95% CI [0.19, 0.81]), of avoiding public transportation (34.5% vs. 60.3%; AOR = 0.42, 95% CI [0.21, 0.83]) and of avoiding traveling overall (32.7% vs. 62.6%; AOR = 0.32, 95% CI [0.16, 0.63]). Parallel findings were observed in analyses of past two-week reported MA use and COVID-19 protective behaviors.

Conclusion

Findings highlight ways in which reported MA use frequency links with avoidance of reported preventive behaviors for COVID-19 in urban diverse MSM. Findings also provide evidence to guide public health interventions in future outbreaks of COVID-19 and other infectious diseases among MSM.

Squamous cell carcinoma of the ovary (SCC) is a rare and aggressive disease and optimal treatment is unknown. Here we report the case of a 29- year-old woman who presented with abdominal pain and was ultimately found to have a multi-septate, gas containing pelvic mass with mixed fat, soft tissue, and calcified components concerning for a ruptured teratoma with fistulization to the distal ileum and cecum on imaging. Operative findings included a 20 cm pelvic mass arising from the right ovary with frank invasion into the ileum and cecum and dense adhesion to the anterior abdominal wall on surgical exploration. Pathologic specimens were remarkable for stage IIIC SCC of the ovary arising in a mature teratoma, with a tumor proportion score of 40%. She progressed on first line treatment with cisplatin, paclitaxel and pembrolizumab as well as second line treatment with gemcitabine and vinorelbine. She died nine months after her initial diagnosis.