Predicting in-hospital mortality risk for perforated peptic ulcer surgery: the PPUMS scoring system and the benefit of laparoscopic surgery: a population-based study.

BACKGROUND: The major treatment for perforated peptic ulcers (PPU) is surgery. It remains unclear which patient may not get benefit from surgery due to comorbidity. This study aimed to generate a scoring system by predicting mortality for patients with PPU who received non-operative management (NOM) and surgical treatment. METHOD: We extracted the admission data of adult (≥ 18 years) patients with PPU disease from the NHIRD database. We randomly divided patients into 80% model derivation and 20% validation cohorts. Multivariate analysis with a logistic regression model was applied to generate the scoring system, PPUMS. We then apply the scoring system to the validation group. RESULT: The PPUMS score ranged from 0 to 8 points, composite with age (< 45: 0 points, 45-65: 1 point, 65-80: 2 points, > 80: 3 points), and five comorbidities (congestive heart failure, severe liver disease, renal disease, history of malignancy, and obesity: 1 point each). The areas under ROC curve were 0.785 and 0.787 in the derivation and validation groups. The in-hospital mortality rates in the derivation group were 0.6% (0 points), 3.4% (1 point), 9.0% (2 points), 19.0% (3 points), 30.2% (4 points), and 45.9% when PPUMS > 4 point. Patients with PPUMS > 4 had a similar in-hospital mortality risk between the surgery group [laparotomy: odds ratio (OR) = 0.729, p = 0.320, laparoscopy: OR = 0.772, p = 0.697] and the non-surgery group. We identified similar results in the validation group. CONCLUSION: PPUMS scoring system effectively predicts in-hospital mortality for perforated peptic ulcer patients. It factors in age and specific comorbidities is highly predictive and well-calibrated with a reliable AUC of 0.785-0.787. Surgery, no matter laparotomy or laparoscope, significantly reduced mortality for scores < = 4. However, patients with a score > 4 did not show this difference, calling for tailored approaches to treatment based on risk assessment. Further prospective validation is suggested.

Engineering stability, longevity, and miscibility of microtubule-based active fluids.

Microtubule-based active matter provides insight into the self-organization of motile interacting constituents. We describe several formulations of microtubule-based 3D active isotropic fluids. Dynamics of these fluids is powered by three types of kinesin motors: a processive motor, a non-processive motor, and a motor which is permanently linked to a microtubule backbone. Another modification uses a specific microtubule crosslinker to induce bundle formation instead of a non-specific polymer depletant. In comparison to the already established system, each formulation exhibits distinct properties. These developments reveal the temporal stability of microtubule-based active fluids while extending their reach and the applicability.

Association Between Recurrent Laryngeal Nerve Calibre and Body Figure: A Preoperative Tool to Assess Thin-Diameter Nerves in Thyroidectomy.

Inadvertent recurrent laryngeal nerve (RLN) injury is a major complication of thyroidectomy. This study aimed to investigate the association between preoperative clinical parameters and RLN size prediction. Total thyroidectomy and thyroid lobectomy data were collected between January 2014 and April 2017. Routine identification of the recurrent laryngeal nerves was performed, while intraoperative findings (nerve diameter, thyroid gland weight, intraoperative neuromonitoring (IONM) use, and signal recording) and demographic data were collected for analysis. A total of 848 patients with 1357 RLNs at risk were enrolled in this study. RLN diameter was thinner in females, those with body height <160 cm, and those with a BMI <25 (all p < 0.001). RLN diameter was directly proportional to age, body weight, height, and BMI. RLN diameter was thinner (1.71 mm vs. 1.55 mm, p = 0.039) and branched nerve incidence was higher (18.5% vs. 29.7%, p = 0.09) in the postoperative RLN injury group. Branched nerves were more frequently encountered in female patients (female vs. male: 28.8% vs. 18.7%, p = 0.004). The risk of RLN palsy in intraoperative IONM loss patients was 27 times higher compared to that in IONM normal patients (1.55% vs. 30%, p < 0.001). Thinner nerves did not yield a higher rate of IONM signal loss. Thinner nerves and higher palsy rates could be anticipated in females, younger age groups, those with shorter stature, and those with low BMI. RLN diameter was not associated with the rate of IONM signal loss.

Collective dynamics of microtubule-based 3D active fluids from single microtubules.

Self-organization of kinesin-driven, microtubule-based 3D active fluids relies on the collective dynamics of single microtubules. However, the connection between macroscopic fluid flows and microscopic motion of microtubules remains unclear. In this work, the motion of single microtubules was characterized by means of 2D gliding assays and compared with the flows of 3D active fluids. While the scales of the two systems differ by ∼1000×, both were driven by processive, non-processive or an equal mixture of both molecular motor proteins. To search for the dynamic correlation between both systems, the motor activities were tuned by varying temperature and ATP concentration, and the changes in both systems were compared. Motor processivity played an important role in active fluid flows but only when the fluids were nearly motionless; otherwise, flows were dominated by hydrodynamic resistance controlled by sample size. Furthermore, while the motors' thermal reaction led active fluids to flow faster with increasing temperature, such temperature dependence could be reversed by introducing temperature-varying depletants, emphasizing the potential role of the depletant in designing an active fluid's temperature response. The temperature response of active fluids was nearly immediate (⪅10 s). Such a characteristic enables active fluids to be controlled with a temperature switch. Overall, this work not only clarifies the role of temperature in active fluid activity, but also sheds light on the underlying principles of the relationship between the collective dynamics of active fluids and the dynamics of their constituent single microtubules.

Polygamous particles.

DNA is increasingly used as an important tool in programming the self-assembly of micrometer- and nanometer-scale particles. This is largely due to the highly specific thermoreversible interaction of cDNA strands, which, when placed on different particles, have been used to bind precise pairs in aggregates and crystals. However, DNA functionalized particles will only reach their true potential for particle assembly when each particle can address and bind to many different kinds of particles. Indeed, specifying all bonds can force a particular designed structure. In this paper, we present the design rules for multiflavored particles and show that a single particle, DNA functionalized with many different "flavors," can recognize and bind specifically to many different partners. We investigate the cost of increasing the number of flavors in terms of the reduction in binding energy and melting temperature. We find that a single 2-µm colloidal particle can bind to 40 different types of particles in an easily accessible time and temperature regime. The practical limit of ∼100 is set by entropic costs for particles to align complementary pairs and, surprisingly, by the limited number of distinct "useful" DNA sequences that prohibit subunits with nonspecific binding. For our 11 base "sticky ends," the limit is 73 distinct sequences with no unwanted overlaps of 5 bp or more. As an example of phenomena enabled by polygamous particles, we demonstrate a three-particle system that forms a fluid of isolated clusters when cooled slowly and an elastic gel network when quenched.

Cinnamate-based DNA photolithography.

As demonstrated by means of DNA nanoconstructs, as well as DNA functionalization of nanoparticles and micrometre-scale colloids, complex self-assembly processes require components to associate with particular partners in a programmable fashion. In many cases the reversibility of the interactions between complementary DNA sequences is an advantage. However, permanently bonding some or all of the complementary pairs may allow for flexibility in design and construction. Here, we show that the substitution of a cinnamate group for a pair of complementary bases provides an efficient, addressable, ultraviolet light-based method to bond complementary DNA covalently. To show the potential of this approach, we wrote micrometre-scale patterns on a surface using ultraviolet light and demonstrated the reversible attachment of conjugated DNA and DNA-coated colloids. Our strategy enables both functional DNA photolithography and multistep, specific binding in self-assembly processes.

Immune Responses to Anti-Hepatitis C Virus Antibodies during Pre-Liver Transplantation Direct-Acting Antiviral Therapy in Hepatitis C Virus-Infected Recipients Associated with Post-Liver Transplantation Allograft Injury.

BACKGROUND AND AIMS: The impact of antibody responses following direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV)-infected recipients before and after liver transplantation (LT) is still undetermined. METHODS: In this observational cohort study, we aimed to explore the association between changes in anti-HCV antibody titers following pre-LT DAA therapy and allograft injury, including biliary complications (BCs) and acute cellular rejection (ACR). RESULTS: A total of 153 cases were enrolled from January 2015 to February 2021. Serum anti-HCV antibody titers were assessed before and after (day 30) LT. Among all recipients, 31/153 (20.3%) had pre-LT DAA therapy (the DAA group) and 122/153 (79.7%) did not undergo pre-LT DAA therapy (the DAA-naïve group). A higher incidence of post-LT BCs was observed in the DAA group (p = 0.028). Compared with the DAA-naïve group, the DAA group had a significantly higher mean level of anti-HCV titer upregulation (p = 0.0024); furthermore, among the recipients with BCs (n = 28) and ACR (n = 41), those in the DAA group exhibited significantly higher mean levels of anti-HCV antibody titer upregulation (p < 0.005). CONCLUSIONS: In conclusion, we speculate that the upregulation of anti-HCV antibody titers, which might have been induced via the restoration of HCV-specific immune responses through pre-LT DAA therapy, was associated with post-LT allograft injury.

Risk factors for gallbladder polyps observed through second-look abdominal sonography in patients with fatty liver disease.

CONCLUSION: FLD, older age group, and alcohol consumption are major risk factors of GBP formation in Taiwanese population. The presence of GBPs might be revealed in second-look examinations of abdominal sonographies.

Self-mixing in microtubule-kinesin active fluid from nonuniform to uniform distribution of activity.

Active fluids have applications in micromixing, but little is known about the mixing kinematics of systems with spatiotemporally-varying activity. To investigate, UV-activated caged ATP is used to activate controlled regions of microtubule-kinesin active fluid and the mixing process is observed with fluorescent tracers and molecular dyes. At low Péclet numbers (diffusive transport), the active-inactive interface progresses toward the inactive area in a diffusion-like manner that is described by a simple model combining diffusion with Michaelis-Menten kinetics. At high Péclet numbers (convective transport), the active-inactive interface progresses in a superdiffusion-like manner that is qualitatively captured by an active-fluid hydrodynamic model coupled to ATP transport. Results show that active fluid mixing involves complex coupling between distribution of active stress and active transport of ATP and reduces mixing time for suspended components with decreased impact of initial component distribution. This work will inform application of active fluids to promote micromixing in microfluidic devices.

Mortality Prediction Model before Surgery for Acute Mesenteric Infarction: A Population-Based Study.

Surgery for acute mesenteric infarction (AMI) is associated with high mortality. This study aimed to generate a mortality prediction model to predict the 30-day mortality of surgery for AMI. We included patients ≥18 years who received bowel resection in treating AMI and randomly divided into the derivation and validation groups. After multivariable analysis, the 'Surgery for acute mesenteric infarction mortality score' (SAMIMS) system was generated and was including age >62-year-old (3 points), hemodialysis (2 points), congestive heart failure (1 point), peptic ulcer disease (1 point), diabetes (1 point), cerebrovascular disease (1 point), and severe liver disease (4 points). The 30-day-mortality rates in the derivation group were 4.4%, 13.4%, 24.5%, and 32.5% among very low (0 point), low (1−3 point(s)), intermediate (4−6 points), and high (7−13 points)-risk patients. Compared to the very-low-risk group, the low-risk (OR = 3.332), intermediate-risk (OR = 7.004), and high-risk groups (OR = 10.410, p < 0.001) exhibited higher odds of 30-day mortality. We identified similar results in the validation group. The areas under the ROC curve were 0.677 and 0.696 in the derivation and validation groups. Our prediction model, SAMIMS, allowed for the stratification of the patients' 30-day-mortality risk of surgery for acute mesenteric infarction.

The serial changes of Neutrophile-Lymphocyte Ratio and correlation to weight loss after Laparoscopic Sleeve Gastrectomy.

Purpose: This study aims to identify the pre- and postoperative changes in the neutrophil-lymphocyte ratio (NLR) and its correlations to clinical characteristics in obese patients who underwent laparoscopic sleeve gastrectomy (LSG). Method: Retrospectively, we included patients who has undergone LSG in our institution between January 2019 and April 2021. A total of 100 patients whose body mass index over 32.5 and received primary laparoscopic sleeve gastrectomy without infectious condition were included. Results: There was a significant decline in NLR (T0 vs. POM3 2.21 vs. 1.78, p = 0.005), neutrophil (T0 vs. POM3 5369 vs. 4050, p < 0.001) and lymphocyte count (T0 vs. POM3 2440: 2100, p < 0.001, respectively) at postoperative 3 months (POM3) compared to preoperative (T0) levels, but similar between POM3 and POM6. The declined counts (Neutrophile vs. Lymphocyte 1445.5/µl vs. 323.5/µl, p < 0.001) and percentage (Neutrophile vs. Lymphocyte 25.11% vs. 13.07%, p < 0.001) of neutrophile are higher than lymphocyte from T0 to POM3, but similar in POM3 and POM6. Preoperative NLR has a significant correlation with the preoperative body weight, preoperative insulin level, and excessive body weight loss (EBWL) at POM3. Preoperative NLR <2.36 had a sensitivity of 67.6% and a specificity of 62.5% in predicting successful weight loss (EBWL > 37.7%) at POM3 (AUC = 0.635, p = 0.032). Conclusion: There was a significant decline in NLR, neutrophil, and lymphocyte count from T0 to POM3, but similar between POM3 and POM6. The declined counts and percentage of neutrophile are higher than lymphocyte. Preoperative NLR shows the potential to be used as a prognostic biomarker for predicting successful weight loss at POM3 after LSG. Further studies could be designed to evaluate the value of prediction in successful outcome after LSG and figure out the relationship between the changes of neutrophil function and oncogenesis.

Immunohistochemistry Staining-Proven Cytomegalovirus Colitis in Living Donor Liver Transplantation.

Background and Aims: Cytomegalovirus (CMV) infection is a common occurrence in liver transplantation (LT) even in an era of preventive strategies. However, the diagnosis of CMV colitis remains challenging. This study aimed to focus on the clinical significance of endoscopic biopsy-proven CMV colitis in patients following living donor liver transplantation (LDLT). Methods: From January 2007 to December 2021, a total of 55 CMV colitis cases were retrospectively enrolled and divided into a non-LDLT group in 53 and an LDLT group in 2 cases. Clinical demographics, diagnostic measurement, histopathology, and anti-viral therapy were investigated. Results: There were 1630 cases undergoing LDLT in the period 2007-2021, with only 2 recipients being confirmed to have CMV colitis in 2021 (2/114, 1-year incidence: 1.75%). Comparisons between the 53 non-LDLT cases and 2 LDLT cases are as follows: Serum anti-CMV immunoglobulin M (IgM) was shown to be positive (n = 3, 5.5% vs. n = 0, p = 1.0) and negative (n = 20, 37.7% vs. n = 2, 100%, p = 0.16); anti-CMV immunoglobulin G (IgG) was positive (n = 19, 35.8% vs. n = 2, 100%, p = 0.14) and none were negative; CMV DNAemia was shown to be detectable (n = 14, 26.4% vs. n = 1, 50%, p = 0.47) and undetectable (n = 14, 26.4% vs. n = 1, 50%, p = 0.47). Among the two recipients with CMV colitis, one had CMV DNAemia and the other had no CMV DNAemia upon the development of symptoms; negative anti-CMV-IgM and positive anti-CMV-IgG were observed both pre-transplant and post-transplant; finally, CMV colitis was documented based on the presence of inclusion bodies and positive immunohistochemistry (IHC) staining in histology. Conclusion: Patients with immunocompromised status, in particular organ transplantation, may have positive serum anti-CMV IgM/IgG antibodies both before and after transplantation. This study emphasized the fact that endoscopic biopsy with IHC staining may be a more powerful tool for making an accurate diagnosis of CMV colitis in the setting of living donor liver transplantation.

Liver Graft MicroRNAs Expression in Different Etiology of Acute Jaundice after Living Donor Liver Transplantation.

Background: Acute jaundice remains a critical problem following liver transplantation. MicroRNAs (miRNAs) are involved in regulating gene expression related to various disease phenotypes and statuses. Aims: To differentiate acute jaundice etiology after living donor liver transplantation (LDLT), we examined the hepatic miRNA expression patterns in several liver graft pathologies. Methods: Eighty liver transplant recipients undergoing post-LDLT graft biopsy for the evaluation of acute jaundice were enrolled in this 1-year prospective study. Using a real-time quantitative reverse transcription-polymerase chain reaction profiling assay, we identified hepatic miRNA (miRNA-122, miRNA-301, miRNA-133a, and miRNA-21) signatures in various allografts pathologies. Results: Pathologic findings of the 80 recipients were as follows: acute cholangitis (AC), 37 (46%); acute rejection (AR), 20 (25%); recurrent hepatitis (RH), 12 (15%); non-specific pathological change, 6 (8%); and fatty change (FC), 5 (6%). None of these identified hepatic miRNAs expression pattern was significantly correlated with serum parameters, including neutrophil-lymphocyte ratio. In AC, hepatic miRNA-122, miRNA-301, miRNA-133a, and miRNA-21 expression was significantly downregulated (p < 0.05). MicroRNA-122 expression was elevated in cases of AR and RH (p < 0.05); miRNA-301 and miRNA-21 expression was higher in RH than in AC (p < 0.05); and miRNA-133a expression was higher in FC than in AR (p < 0.05). Conclusions: Our study suggests that specific hepatic miRNA expression patterns as a checklist may be useful for differential diagnosis of acute jaundice following liver transplantation.

Flow coupling between active and passive fluids across water-oil interfaces.

Active fluid droplets surrounded by oil can spontaneously develop circulatory flows. However, the dynamics of the surrounding oil and their influence on the active fluid remain poorly understood. To investigate interactions between the active fluid and the passive oil across their interface, kinesin-driven microtubule-based active fluid droplets were immersed in oil and compressed into a cylinder-like shape. The droplet geometry supported intradroplet circulatory flows, but the circulation was suppressed when the thickness of the oil layer surrounding the droplet decreased. Experiments with tracers and network structure analyses and continuum models based on the dynamics of self-elongating rods demonstrated that the flow transition resulted from flow coupling across the interface between active fluid and oil, with a millimeter-scale coupling length. In addition, two novel millifluidic devices were developed that could trigger and suppress intradroplet circulatory flows in real time: one by changing the thickness of the surrounding oil layer and the other by locally deforming the droplet. This work highlights the role of interfacial dynamics in the active fluid droplet system and shows that circulatory flows within droplets can be affected by millimeter-scale flow coupling across the interface between the active fluid and the oil.

Effects of confinement on the dynamics and correlation scales in kinesin-microtubule active fluids.

We study the influence of solid boundaries on dynamics and structure of kinesin-driven microtubule active fluids as the height of the container, H, increases from hundreds of micrometers to several millimeters. By three-dimensional tracking of passive tracers dispersed in the active fluid, we observe that the activity level, characterized by velocity fluctuations, increases as system size increases and retains a small-scale isotropy. Concomitantly, as the confinement level decreases, the velocity-velocity temporal correlation develops a strong positive correlation at longer times, suggesting the establishment of a "memory". We estimate the characteristic size of the flow structures from the spatial correlation function and find that, as the confinement becomes weaker, the correlation length, l_{c}, saturates at approximately 400 microns. This saturation suggests an intrinsic length scale which, along with the small-scale isotropy, demonstrates the multiscale nature of this kinesin-driven bundled microtubule active system.

Scarless Completion Thyroidectomy After Initial Transoral Approach for Differentiated Thyroid Cancer: How and When to Start?

BACKGROUND: With growing literature, the feasibility of transoral endoscopic thyroidectomy vestibular approach (TOETVA) has been confirmed as a valid method for managing differentiated thyroid cancer. Completion thyroidectomy (CT) is recommended in patients who have been diagnosed with differentiated thyroid cancer after unilateral lobectomy by TOETVA. In this retrospective study, the authors addressed the critical questions of how and when to do the second operation of CT to avoid a neck scar. MATERIALS AND METHODS: The authors retrospectively reviewed our patients who had received TOETVA in our hospital from August 2016 to December 2019. Those who received CT after initial TOETVA as cTOETVA were further separated according to the approaching methods. Demographic data, operative variables, and postoperative variables were collected and analyzed. RESULTS: A total of 97 patients were enrolled using TOETVA. Malignancies were present in 42 patients (43.3%) using TOETVA. There were 3 approaching methods of cTOETVA and separated into reopen transcervical approach (re-TCA), retransoral TOETVA (re-TOETVA), and transaxillary approach (TAA) groups. There were no significant complications among patients for cTOETVA. Of the 8 patients for the cTOETVA, 3 received re-TCA, 3 re-TOETVA, and 2 TAA. CONCLUSIONS: The outcomes are encouraging and demonstrate the feasibility of scarless completion thyroidectomy after initial TOETVA. The re-TOETVA procedure should be completed within 14 days after the initial TOETVA procedure, TAA beyond 14 days, and re-TCA may be completed at any time. The cTOETVA techniques using re-TOETVA or TAA have better cosmetic results than re-TCA in oncological equivalency.

HCV RNA in serum and liver samples of patients undergoing living donor liver transplantation.

OBJECTIVE: To compare hepatitis C virus (HCV) RNA levels from serum and explanted native liver samples from patients undergoing living donor liver transplantation (LDLT). METHODS: This was a prospective observational study. Serum and liver samples were collected from consecutive serum anti-HCV-positive transplant recipients between February 2016 to August 2019. HCV RNA was extracted from liver samples and subjected to one-step reverse-transcription qPCR. using the TopScript One Step qRT-PCR Probe Kit with HCV qPCR probe assay and human GAPDH qPCR probe assay on a ViiA7 Real-Time PCR System. RESULTS: Among the 80 patients, 36% (29/80) were HCV RNA positive in serum and 85% (68/80) had positive hepatic HCV RNA. Post-liver transplantation, 4% (3/80) patients were serum positive. CONCLUSIONS: Our study suggests that pre-transplant serum HCV RNA levels may give an underestimate of the number of positive HCV RNA cases and that hepatic HCV RNA data may be more accurate.

Controlling Flow Speeds of Microtubule-Based 3D Active Fluids Using Temperature.

We present a method for using temperature to tune the flow speeds of kinesin-driven, microtubule-based three-dimensional (3D) active fluids. This method allows for tuning the speeds in situ without the need to manufacture new samples to reach different desired speeds. Moreover, this method enables the dynamic control of speed. Cycling the temperature leads the fluids to flow fast and slow, periodically. This controllability is based on the Arrhenius characteristic of the kinesin-microtubule reaction, demonstrating a controlled mean flow speed range of 4-8 µm/s. The presented method will open the door to the design of microfluidic devices where the flow rates in the channel are locally tunable without the need for a valve.

Transition from turbulent to coherent flows in confined three-dimensional active fluids.

Transport of fluid through a pipe is essential for the operation of macroscale machines and microfluidic devices. Conventional fluids only flow in response to external pressure. We demonstrate that an active isotropic fluid, composed of microtubules and molecular motors, autonomously flows through meter-long three-dimensional channels. We establish control over the magnitude, velocity profile, and direction of the self-organized flows and correlate these to the structure of the extensile microtubule bundles. The inherently three-dimensional transition from bulk-turbulent to confined-coherent flows occurs concomitantly with a transition in the bundle orientational order near the surface and is controlled by a scale-invariant criterion related to the channel profile. The nonequilibrium transition of confined isotropic active fluids can be used to engineer self-organized soft machines.

Kinetics of DNA-coated sticky particles.

DNA-functionalized particles are promising for complex self-assembly due to their specific controllable thermoreversible interactions. However, there has been little work on the kinetics and the aggregation rate, which depend on the rate of particle encounters and the probability that an encounter results in particles sticking. In this study, we investigate theoretically and experimentally the aggregation times of micron-scale particles as a function of DNA coverage and salt concentration. Our 2-µm colloids accommodate up to 70,000 DNA strands. For full coverage and high salt concentration, the aggregation time is 5 min while for 0.1 coverage and low salt it is 4 days. A simple model using reaction-limited kinetics and experimental oligomer hybridization rates describes the data well. A controlling factor is the Coulomb barrier at the nanometer scale retarding DNA hybridization. Our model allows easy measurements of microscopic hybridization rates from macroscopic aggregation and enables the design of complex self-assembly schemes with controlled kinetics.