Prolapse repair after anterior exenteration.

This report presents our experience in performing prolapse repair after anterior exenteration. The patient had a history of invasive bladder cancer and underwent a robotically assisted laparoscopic anterior exenteration with extended bilateral pelvic lymph node dissection and creation of an Indiana pouch continent diversion. Her pelvic organ prolapse progressed over time despite multiple pessary fittings. She eventually decided to proceed with pelvic reconstructive surgery 6 years after her cancer surgery. She underwent a successful vaginal native tissue reconstruction with uterosacral ligament suspension, posterior repair and reconstruction of the anterior compartment. The patient has been followed for 16 months without recurrent prolapse. Vaginal native tissue pelvic reconstruction is feasible in a patient with a history of pelvic exenteration.

Single limb electrocardiogram using vector mapping: Evaluation and validation of a novel medical device.

INTRODUCTION: The Tiger Tech Warfighter Monitor (WFM) is a novel single-limb device for ECG acquisition. The WFM provides true (not derived) single limb Electrocardiogram monitoring (ECG) to provide heart rate and R-R interval monitoring between QRS complexes. Herein, we evaluate the diagnostic accuracy of the WFM heart rate, R-R interval monitoring, and heart rate variability monitoring in comparison to a 2­lead chest ECG. METHODS: Data was collected under Institutional Review Board (IRB) approval. Patients available within our institution's pre-operative holding unit were randomly selected to undergo simultaneous chest and WFM ECG monitoring. 3-5-min measurements were taken depending on the patient's availability. Data was saved to two separate mobile phones and time-stamped for synchronization. A proprietary Tiger Tech extraction algorithm was used to tag proper features on both the WFM 1-Limb ECG and Chest ECG data files. A separate algorithm was then used to compare the beat-to-beat variations between the ECGs. RESULTS: Data was extracted and analyzed on 26 subjects. Linear regression of heart rate analysis revealed excellent correlations with an R2 of 0.99 (p < 0.05). Similar linear regression evaluation of R-R interval correlation demonstrated a mean R2 value of 0.95 (p < 0.05). Statistically significant correlation was achieved in all 26 included study participants. Heart rate variability also achieved excellent correlation (SDNN R2 = 0.997, RMSSD R2 = 0.995, LnRMSSD R2 = 0.992, p << 0.05). CONCLUSION: Results demonstrate that the WFM achieves excellent correlation with chest ECG for heart rate, R-R internals, and heart rate variability.

Silylpalladium Cations Enable the Oxidative Addition of C(sp3)-O Bonds.

The synthesis and characterization of the room-temperature and solution-stable silylpalladium cations (PCy3)2Pd-SiR3+(C6F5)4B- (SiR3 = SiMe2Et, SiHEt2) and (Xantphos)Pd-SiR3+(BArf4) (SiR3 = SiMe2Et, SiHEt2; Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; BArf4 = (3,5-(CF3)2C6H3)4B-) are reported. Spectroscopic and ligand addition experiments suggest that silylpalladium complexes of the type (PCy3)2Pd-SiR3+ are three-coordinate and T-shaped. Addition of dialkyl ethers to both the PCy3 and Xantphos-based silylpalladium cations resulted in the cleavage of C(sp3)-O bonds and the generation of cationic Pd-alkyl complexes. Mechanistically enabling is the ability of silylpalladium cations to behave as sources of both electrophilic silylium ions and nucleophilic LnPd(0).

The Comprehensive Complication Index: a New Measure of the Burden of Complications After Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) are complex surgeries with multiple comorbidities. The Clavien-Dindo classification (CDC) is the most commonly used method to report surgical morbidity, but limits it to the highest-grade complication. The Comprehensive Complication Index (CCI) is a score ranging from 0 to 100, calculated using all 30-day complications and their treatment after abdominal surgery. The aim of this study is to assess the CCI's validity in the HIPEC patient population. METHODS: A review of our institutional cytoreduction database from 2009 to 2015 was undertaken. Patient demographics, pathology, Peritoneal Carcinomatosis Index (PCI), complications and their treatments, and length of stay (LOS) were reviewed. The CCI was calculated for each patient. Linear regression was used to assess whether the CCI and CDC were predictors of LOS. RESULTS: Of 157 patients reviewed, 110 (70.1%) underwent HIPEC. The majority were female (77, 66.9%), and the mean age was 53.7 years. Mean PCI was 13.2 [interquartile range (IQR) 7-18]. Median CDC was grade 2 (IQR 0-2), and only 9.8% had CDC of grade 4 or higher. Mean CCI was 21.4, while the median was 20.9 (IQR 0-30.8). Mean LOS was 16.2 days, while the median was 11 days (IQR 8-15 days). The CCI strongly correlated with LOS with coefficient of 0.46 [95% confidence interval (CI) 0.38-0.54, p = 0.000]. CONCLUSIONS: The CCI is an adequate tool to capture all complications and their overall burden in patients having undergone HIPEC. This study shows that the CCI can predict LOS and could be used to quantify and compare the burden of multiple complications.

A collaborative surgical approach to upper and lower abdominal cytoreductive surgery in ovarian cancer.

BACKGROUND AND OBJECTIVES: Cytoreductive surgery with complete macroscopic resection in patients with ovarian cancer is associated with improved survival. Institutional reports of combined upper and lower abdominal cytoreductive surgery for more advanced disease have described multidisciplinary approaches. We sought to investigate outcomes in patients undergoing cytoreductive surgery in patients with upper and lower abdominal disease at our institution. METHODS: Patients who underwent cytoreductive surgery for ovarian malignancies from 2008 to 2015 were retrospectively identified from an institutional database. Upper abdominal cytoreduction was defined anatomically as debulking of disease proximal to the ligament of Treitz. Perioperative outcomes were analyzed. RESULTS: A total of 258 operations were performed, the majority for serous ovarian carcinoma (70%). The gynecologic oncologist was the primary surgeon and often assisted by either a surgical oncology fellow and/or attending. In operations with combined upper and lower abdominal cytoreduction, patients were more likely to have an American society of anesthesiologists physical status classification system (ASA) of 3, peritoneal implants, and liver/spleen metastases. Preoperative chemotherapy and optimal cytoreduction were similar between groups. Perioperative morbidity and mortality were not significantly different between groups. CONCLUSIONS: A collaborative surgical approach to combined upper and lower abdominal cytoreductive surgery in patients with ovarian cancer should be performed, if needed, to achieve an optimal cytoreduction.

Concurrent pelvic reconstruction and minimally invasive pelvic cancer surgery.

INTRODUCTION AND HYPOTHESIS: We present our experience in performing concurrent prolpase repair at the time of gynecologic cancer surgery. METHODS: The uterosacral ligaments are tagged before performing hysterectomy and pelvic dissection. The uterosacral ligament suspensory sutures are then placed laparoscopically after completion of pelvic cancer surgery. The remainder of the prolapse surgery is performed through a transvaginal approach. RESULTS: Many of our patients who undergo concurrent prolapse repair and gynecolgical cancer surgery receive chemotherapy and pelivc radiation. Concuurent prolapse repair improves their prolaspe symptoms. CONCLUSION: Concurrent prolapse repair should be performed at the same time as gynecologic cancer surgery.

Base Excess as a Predictor of Complications in Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Base excess is important in assessing metabolic status. Postoperative management in patients undergoing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancies can be a challenge, and we therefore sought to investigate perioperative predictors of overall morbidity in CRS/HIPEC patients at our institution. METHODS: Patients who underwent CRS/HIPEC from 2012 to 2016 were identified retrospectively from a prospectively collected institutional database. Patient demographics and perioperative variables were obtained and the comprehensive complication index (CCI) was calculated for each patient in order to assess perioperative morbidity. Stepwise linear regression analyses were performed, with CCI as the outcome variable. RESULTS: A total of 72 CRS/HIPEC patients had recorded base excesses in the first 48 h postoperatively. Mean immediate postoperative base excess was -6.0 mmol/L (interquartile range [IQR] -8 to -4.1), mean delta base excess at 48 h was +4.3 mmol/L (IQR +2.1 to +6.2), and mean CCI was 25.2 (IQR 8.7-36.7). On multivariate analysis, delta base excess was the only significant predictor of CCI, demonstrating a protective effect (p = 0.001). In patients who experienced less than the mean delta base excess of +4.3 mmol/L, lower delta base excess was an independent predictor of complications (p < 0.001). CONCLUSIONS: Delta base excess is an independent predictor of morbidity in patients undergoing CRS/HIPEC. A delta base excess of greater than +4.3 mmol/L at 48 h may be an appropriate goal for resuscitation of CRS/HIPEC patients in the immediate postoperative period. Standardized protocols to correct the base deficit in CRS/HIPEC patients during the early postoperative period can potentially help mitigate perioperative morbidity.

Surgical Management of Vulvar Cancer.

Vulvar cancer is a rare malignancy with high curability in early-stage disease, yet poor outcomes for advanced-stage and recurrent disease. Surgical management is at the cornerstone of treatment for most vulvar cancers, and includes conservative and radical resection of the primary vulvar tumor and excision of local lymph nodes, which are major prognostic factors and drive adjuvant treatment. This review summarizes the surgical management of primary squamous cell carcinoma of the vulva, specifically initial treatment guidelines by stage, based on the 2017 NCCN Clinical Practice Guidelines in Oncology for Vulvar Cancer.

Investigation of a Catenane with a Responsive Noncovalent Network: Mimicking Long-Range Responses in Proteins.

We report a functional synthetic model for studying the noncovalent networks (NCNs) required for complex protein functions. The model [2]-catenane is self-assembled from dipeptide building blocks and contains an extensive network of hydrogen bonds and aromatic interactions. Perturbations to the catenane cause compensating changes in the NCNs structure and dynamics, resulting in long-distance changes reminiscent of a protein. Key findings include the notion that NCNs require regions of negative cooperativity, or "frustrated" noncovalent interactions, as a source of potential energy for driving the response. We refer to this potential energy as latent free energy and describe a mechanistic and energetic model for responsive systems.

A catalyst selection protocol that identifies biomimetic motifs from ß-hairpin libraries.

Assaying a solid-phase library of histidine-containing ß-hairpin peptides by a reactive tagging scheme in organic solvents selects for catalysts that reproduce the strategies used by His-based enzyme active sites to accelerate acyl- and phosphonyl-transfer reactions. Rate accelerations (k(rel)) in organic solvents of up to 2.4 × 10(8) are observed.

The feasibility and safety of same-day discharge after robotic-assisted hysterectomy alone or with other procedures for benign and malignant indications.

OBJECTIVE: This study aimed to report the feasibility and safety of same-day discharge after robotic-assisted hysterectomy. METHODS: Same-day discharge after robotic-assisted hysterectomy was initiated 07/2010. All cases from then through 12/2012 were captured for quality assessment monitoring. The distance from the hospital to patients' homes was determined using http://maps.google.com. Procedures were categorized as simple (TLH+/-BSO) or complex (TLH+/-BSO with sentinel node mapping, pelvic and/or aortic nodal dissection, appendectomy, or omentectomy). Urgent care center (UCC) visits and readmissions within 30days of surgery were captured, and time to the visit was determined from the initial surgical date. RESULTS: Same-day discharge was planned in 200 cases. Median age was 52years (range, 30-78), BMI was 26.8kg/m(2) (range, 17.4-56.8), and ASA was class 2 (range, 1-3). Median distance traveled was 31.5miles (range, 0.2-149). Procedures were simple in 109 (55%) and complex in 91 (45%) cases. The indication for surgery was: endometrial cancer (n=82; 41%), ovarian cancer (n=5; 2.5%), cervical cancer (n=8; 4%), and non-gynecologic cancer/benign (n=105; 53%). One hundred fifty-seven (78%) had successful same-day discharge. Median time for discharge for these cases was 4.8h (range, 2.4-10.3). Operative time, case ending before 6pm, and use of intraoperative ketorolac were associated with successful same-day discharge. UCC visits occurred in 8/157 (5.1%) same-day discharge cases compared to 5/43 (11.6%) requiring admission (P=.08). Readmission was necessary in 4/157 (2.5%) same-day discharge cases compared to 3/43 (7.0%) requiring admission (P=.02). CONCLUSIONS: Same-day discharge after robotic-assisted hysterectomy for benign and malignant conditions is feasible and safe.

A comparison of primary intraperitoneal chemotherapy to consolidation intraperitoneal chemotherapy in optimally resected advanced ovarian cancer.

OBJECTIVE: To compare survival outcomes for patients with advanced epithelial ovarian cancer (EOC) who received primary intravenous/intraperitoneal (IV/IP) chemotherapy to those who received IV followed by consolidation (treatment given to patients in remission) IP chemotherapy. METHODS: Data were analyzed and compared for all patients with stage III-IV EOC who underwent optimal primary cytoreduction (residual disease ≤ 1 cm) followed by cisplatin-based consolidation IP chemotherapy (1/2001-12/2005) or primary IV/IP chemotherapy (1/2005-7/2011). RESULTS: We identified 224 patients; 62 (28%) received IV followed by consolidation IP chemotherapy and 162 (72%) received primary IV/IP chemotherapy. The primary IP group had significantly more patients with serous tumors. The consolidation IP group had a significantly greater median preoperative platelet count, CA-125, and amount of ascites. There were no differences in residual disease at the end of cytoreduction between both groups. The median progression-free survival (PFS) was greater for the primary IP group; however, this did not reach statistical significance (23.7 months vs 19.7 months; HR 0.78; 95% CI, 0.57-1.06; p=0.11). The median overall survival (OS) was significantly greater for the primary IP group (78.8 months vs 57.5 months; HR 0.56; 95% CI, 0.38-0.83; p=0.004). On multivariate analysis, after adjusting for confounders, the difference in PFS was not significant (HR 0.78; 95% CI, 0.56-1.11; p=0.17), while the difference in OS remained significant (HR 0.59; 95% CI, 0.39-0.89; p=0.01). CONCLUSIONS: In our study, primary IV/IP chemotherapy was associated with improved OS compared to IV followed by consolidation IP chemotherapy in patients with optimally cytoreduced advanced EOC.

Selective transamidation of 3-oxo-N-acyl homoserine lactones by hydrazine derivatives.

A method for the selective transamidation of the 3-oxo sub-family of N-acyl homoserine lactones (3-oxo-AHLs) under physiologically relevant conditions has been developed. The reaction has the potential to serve as a strategy for selective knockdown of key autoinducers in a multicellular environment.

Identification and optimization of short helical peptides with novel reactive functionality as catalysts for acyl transfer by reactive tagging.

Herein we describe the screening and subsequent optimization of peptide catalysts for ester activation. A combinatorial methodology using dye-tagged substrate analogs is described for determining which components of a His-containing helical library display acyl transfer activity. We found that helical peptides display high activity, and amino acids that reinforce this propensity are advantaged. Through this approach two new structural motifs have been discovered that are capable of activating esters in organic solvents. Unlike most acyl transfer catalysts functioning in organic solvents, these catalysts are histidine- rather than N-alkyl histidine-based. Longer peptides with localization of reactive groups on the C-terminal end of the peptide were found to further enhance catalytic activity up to ∼2800-fold over background.

Tracking Cancer: Exploring Heart Rate Variability Patterns by Cancer Location and Progression.

Reduced heart rate variability (HRV) is an autonomic nervous system (ANS) response that may indicate dysfunction in the human body. Consistent evidence shows cancer patients elicit lower HRV; however, only select cancer locations were previously evaluated. Thus, the aim of the current study was to explore HRV patterns in patients diagnosed with and in varying stages of the most prevalent cancers. At a single tertiary academic medical center, 798 patients were recruited. HRV was measured via an armband monitor (Warfighter MonitorTM, Tiger Tech Solutions, Inc., Miami, FL, USA) equipped with electrocardiographic capabilities and was recorded for 5 to 7 min with patients seated in an upright position. Three time-domain metrics were calculated: SDNN (standard deviation of the NN interval), rMSSD (the root mean square of successive differences of NN intervals), and the percentage of time in which the change in successive NN intervals exceeds 50ms within a measurement (pNN50). Of the 798 patients, 399 were diagnosed with cancer. Cancer diagnoses were obtained via medical records one week following the measurement. Analysis of variance models were performed comparing the HRV patterns between different cancers, cancer stages (I-IV), and demographic strata. A total of 85% of the cancer patients had breast, gastrointestinal, genitourinary, or respiratory cancer. The cancer patients were compared to a control non-cancer patient population with similar patient size and distributions for sex, age, body mass index, and co-morbidities. For all HRV metrics, non-cancer patients exhibited significantly higher rMSSDs (11.1 to 13.9 ms, p < 0.0001), SDNNs (22.8 to 27.7 ms, p < 0.0001), and pNN50s (6.2 to 8.1%, p < 0.0001) compared to stage I or II cancer patients. This significant trend was consistently observed across each cancer location. Similarly, compared to patients with stage III or IV cancer, non-cancer patients possessed lower HRs (-11.8 to -14.0 bpm, p < 0.0001) and higher rMSSDs (+31.7 to +32.8 ms, p < 0.0001), SDNNs (+45.2 to +45.8 ms), p < 0.0001, and pNN50s (19.2 to 21.6%, p < 0.0001). The HR and HRV patterns observed did not significantly differ between cancer locations (p = 0.96 to 1.00). The depressed HRVs observed uniformly across the most prevalent cancer locations and stages appeared to occur independent of patients' co-morbidities. This finding highlights the potentially effective use of HRV as a non-invasive tool for determining common cancer locations and their respective stages. More studies are needed to delineate the HRV patterns across different ages, between sexes and race/ethnic groups.

Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1.

Programmed death-ligand 1 (PD-L1) drives inhibition of antigen-specific T cell responses through engagement of its receptor programmed death-1 (PD-1) on activated T cells. Overexpression of these immune checkpoint proteins in the tumor microenvironment has motivated the design of targeted antibodies that disrupt this interaction. Despite clinical success of these antibodies, response rates remain low, necessitating novel approaches to enhance performance. Here, we report the development of antibody fusion proteins that block immune checkpoint pathways through a distinct mechanism targeting molecular trafficking. By engaging multiple receptor epitopes on PD-L1, our engineered multiparatopic antibodies induce rapid clustering, internalization, and degradation in an epitope- and topology-dependent manner. The complementary mechanisms of ligand blockade and receptor downregulation led to more durable immune cell activation and dramatically reduced PD-L1 availability in mouse tumors. Collectively, these multiparatopic antibodies offer mechanistic insight into immune checkpoint protein trafficking and how it may be manipulated to reprogram immune outcomes.

Heat stress from current and predicted increases in temperature impairs lambing rates and birth weights in the Australian sheep flock.

Livestock heat stress threatens production, particularly in semi-arid, arid and tropical regions. Using established temperature thresholds for sheep, we modelled +1 °C and +3 °C temperature increases over the historical baseline, estimating that 2.1 million potential lambs are lost annually due to heat stress alone, increasing to 2.5 and 3.3 million, respectively, as temperatures rise. Heat stress poses risks at key periods of the reproductive cycle, with consequences across the Australian sheep flock.

COVID-19-Induced Changes in Photoplethysmography.

INTRODUCTION: Photoplethysmography (PPG) is the science behind many commonly used medical devices such as the pulse oximeter. PPG changes, herein as "PPG dropouts," have been described in existing in vitro studies following artificially induced clot activation. Because COVID-19 causes increased arterial, venous, and microvascular clot formation, our hypothesis is that PPG dropouts identified in vitro can also be found in vivo in patients with COVID-19. The aim of this study is to evaluate PPG recordings and D-dimer levels for patients hospitalized with COVID-19 and compare them with the PPG tracings from non-COVID controls. MATERIALS AND METHODS: PPG recordings were obtained for 197 ICU patients with COVID-19 and 300 non-COVID controls. PPG tracings were obtained using a TigerTech CovidPlus monitor, which received U.S. FDA emergency use authorization in March 2020 for monitoring the biometrics of patients with COVID-19 and featured unfiltered red and infrared spectrum PPG monitoring. D-dimer lab results were also recorded whenever available. RESULTS: The results demonstrated significant differences in the prevalence rate of PPG dropout among patients with COVID-19 vs. non-COVID controls. The median PPG dropout rate was 0.58 for COVID-19 patients (median 0.58, IQR 0.42-0.72, P < .05) as opposed to a median 0.0 for non-COVID patients (median 0.0, IQR 0.0-0.0, P < .05). Furthermore, at least one incidence of PPG dropout was detected in 100% of COVID-19 patients, as opposed to 2.3% of non-COVID controls (P < .05). PPG dropout also correlated closely with the normalized serum D-dimer levels taken on the same day. The change in the normalized D-dimer levels was plotted against the change in PPG dropout, and a line of best fit was created. Linear regression resulted in R2 = 0.743 (P < .05), indicating that changes in the PPG dropout rate correlate with hemorheological changes in COVID-19 patients. CONCLUSIONS: PPG dropout, like D-dimer, may not be specific for COVID-19. However, the inflammatory nature of the disease and the prevalence of prolonged ICU created a large sample size and allowed the authors to observe PPG changes in vivo in a statistically meaningful way. Further confirmatory studies are needed to confirm the potential application of PPG dropout as a measure of inflammation in other disease processes.

Deep learning enables satellite-based monitoring of large populations of terrestrial mammals across heterogeneous landscape.

New satellite remote sensing and machine learning techniques offer untapped possibilities to monitor global biodiversity with unprecedented speed and precision. These efficiencies promise to reveal novel ecological insights at spatial scales which are germane to the management of populations and entire ecosystems. Here, we present a robust transferable deep learning pipeline to automatically locate and count large herds of migratory ungulates (wildebeest and zebra) in the Serengeti-Mara ecosystem using fine-resolution (38-50 cm) satellite imagery. The results achieve accurate detection of nearly 500,000 individuals across thousands of square kilometers and multiple habitat types, with an overall F1-score of 84.75% (Precision: 87.85%, Recall: 81.86%). This research demonstrates the capability of satellite remote sensing and machine learning techniques to automatically and accurately count very large populations of terrestrial mammals across a highly heterogeneous landscape. We also discuss the potential for satellite-derived species detections to advance basic understanding of animal behavior and ecology.