Background
Cytoreductive surgery (CRS) for colorectal cancer peritoneal carcinomatosis has been shown to prolong survival with acceptable morbidity rates. Total pelvic peritonectomy (TPP), or ...complete removal of all pelvic peritoneum, constitutes an important and technically challenging component of CRS. Here we report our experience and describe our technique of laparoscopic total pelvic peritonectomy (LTPP), using a photographic/videographic step-by-step guide.
Methods
All patients who underwent LTPP for pelvic carcinomatosis from a colorectal origin were included in the study. Only patients with peritoneal cancer index (PCI) score of ≤ 10 were selected for CRS with LTPP. Patients who had extra-abdominopelvic cavity metastases were excluded. The final decision to proceed with CRS was made following laparoscopic assessment.
Results
From January 2017 to December 2020, 15 consecutive patients underwent LTPP for colorectal cancer pelvic carcinomatosis. Median patient age and PCI score was 53 years (range 33–78) and 8 (range 3–10), respectively. Complete cytoreduction was achieved in all patients. Thirteen patients (87%) underwent concomitant hyperthermic intraperitoneal chemotherapy (HIPEC). The median operative duration was 748 min (interquartile range IQR 681–850). Median intra-operative blood loss and length of hospital stay was 100 ml (IQR 50–300) and 10 days (IQR 8–12), respectively. Five patients (33%) experienced 30-day post-operative morbidity, with one (6.7%) experiencing a higher grade (Clavien–Dindo IIIa) complication. Median follow-up duration was 13 months (IQR 3–19), during which four (27%) had systemic recurrence and one (6.7%) died after 15 months following peritoneal and systemic recurrences.
Conclusion
LTPP is a feasible option for low-volume pelvic carcinomatosis from colorectal cancer, offering the benefits of a minimally invasive approach. Strict patient selection is essential, and the procedure should be converted if the PCI score cannot be assessed or complete cytoreduction cannot be achieved. Proficiency at laparoscopic pelvic surgery is mandatory for performing LTPP.
Background Accumulated evidence suggest that specific patterns of histone posttranslational modifications (PTMs) and their crosstalks may determine transcriptional outcomes. However, the regulatory ...mechanisms of these "histone codes" in plants remain largely unknown. Results In this study, we demonstrate for the first time that a salinity stress inducible PHD (plant homeodomain) finger domain containing protein GmPHD5 can read the "histone code" underlying the methylated H3K4. GmPHD5 interacts with other DNA binding proteins, including GmGNAT1 (an acetyl transferase), GmElongin A (a transcription elongation factor) and GmISWI (a chromatin remodeling protein). Our results suggest that GmPHD5 can recognize specific histone methylated H3K4, with preference to di-methylated H3K4. Here, we illustrate that the interaction between GmPHD5 and GmGNAT1 is regulated by the self-acetylation of GmGNAT1, which can also acetylate histone H3. GmGNAT1 exhibits a preference toward acetylated histone H3K14. These results suggest a histone crosstalk between methylated H3K4 and acetylated H3K14. Consistent to its putative roles in gene regulation under salinity stress, we showed that GmPHD5 can bind to the promoters of some confirmed salinity inducible genes in soybean. Conclusion Here, we propose a model suggesting that the nuclear protein GmPHD5 is capable of regulating the crosstalk between histone methylation and histone acetylation of different lysine residues. Nevertheless, GmPHD5 could also recruit chromatin remodeling factors and transcription factors of salt stress inducible genes to regulate their expression in response to salinity stress.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic hepatitis B (CHB) infection is rarely eradicated by current antiviral nucleos(t)ide analogues. We found that alpha2,6-biantennary sialoglycans of HBV surface antigen (HBsAg) bound human ...SIGLEC-3 (CD33) by IP and ELISA, and the binding affinity between SIGLEC-3 and alpha2,6-biantennary sialoglycans was determined by biolayer interferometry (equilibrium dissociation constant KD: 1.95 * 10.sup.-10 + or - 0.21 * 10.sup.-10 M). Moreover, HBV activated SIGLEC-3 on myeloid cells and induced immunosuppression by stimulating immunoreceptor tyrosine-based inhibitory motif phosphorylation and SHP-1/-2 recruitment via alpha2,6-biantennary sialoglycans on HBsAg. An antagonistic anti-SIGLEC-3 mAb reversed this effect and enhanced cytokine production in response to TLR-7 agonist GS-9620 in PBMCs from CHB patients. Moreover, anti-SIGLEC-3 mAb alone was able to upregulate the expression of molecules involved in antigen presentation, such as CD80, CD86, CD40, MHC-I, MHC-II, and PD-L1 in CD14.sup.+ cells. Furthermore, SIGLEC-3 SNP rs12459419 C, which expressed a higher amount of SIGLEC-3, was associated with increased risk of hepatocellular carcinoma (HCC) in CHB patients (HR: 1.256, 95% CI: 1.027-1.535, P = 0.0266). Thus, blockade of SIGLEC-3 is a promising strategy to reactivate host immunity to HBV and lower the incidence of HCC in the CHB patient population.
Herein, we suggest a unique approach to control the handedness of twisted lamellae in banded spherulites of a stereoregular polymer, isotactic poly(2‐vinylpyridine) (iP2VP). When (R)‐ or ...(S)‐hexahydromandelic acid (HMA), which can associate with iP2VP, was introduced as a chiral dopant, mirror‐image CD spectra in the complex systems showed induced circular dichroism (ICD) of the iP2VP by chiral HMA. Banded spherulites resulting from lamellar twisting due to the imbalanced stresses at the opposite folding surfaces could be formed by crystallization of the iP2VP/HMA complexes, which had a crystalline structure similar to that of neat iP2VP. A preferential sense of the twisted crystalline lamellae was found in the iP2VP/HMA complex, thus suggesting homochiral evolution from conformational to hierarchical chirality.
Not just a pretty pattern: The handedness of twisted lamellae in the banded spherulites of isotactic poly(2‐vinylpyridine) (iP2VP) was controlled by the crystallization of iP2VP with chiral dopants (see polarized‐light micrographs). Hexahydromandelic acid (HMA) induced circular dichroism in iP2VP. The mirror‐image CD spectra observed with (R)‐ and (S)‐HMA suggest homochiral evolution from conformational to hierarchical chirality in this system.
A micromachined reconfigurable metamaterial is presented, whose unit cell consists of a pair of asymmetric split‐ring resonators (ASRRs); one is fixed to the substrate while the other is patterned on ...a movable frame. The reconfigurable metamaterial and the supporting structures (e.g., microactuators, anchors, supporting frames, etc.) are fabricated on a silicon‐on‐insulator wafer using deep reactive‐ion etching (DRIE). By adjusting the distance between the two ASRRs, the strength of dipole–dipole coupling can be tuned continuously using the micromachined actuators and this enables tailoring of the electromagnetic response. The reconfiguration of unit cells endows the micromachined reconfigurable metamaterials with unique merits such as electromagnetic response under normal incidence and wide tuning of resonant frequency (measured as 31% and 22% for transverse electric polarization and transverse magnetic polarization, respectively). The reconfiguration could also allow switching between the polarization‐dependent and polarization‐independent states. With these features, the micromachined reconfigurable metamaterials may find potential applications in transformation optics devices, sensors, intelligent detectors, tunable frequency‐selective surfaces, and spectral filters.
A micromachined reconfigurable metamaterial is presented by reconfiguring the unit cell that consists of a pair of asymmetric split‐ring resonators (ASRRs). The material shows wide dynamic tuning of resonant frequency for transverse electric (TE) and transverse magnetic (TM) polarization by changing the separation distance of the two ASRRs and has potential applications in transformation optics devices, sensors, intelligent detectors, and tunable frequency‐selective surfaces.
Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of ...CHC.BACKGROUNDChronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC.The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events.METHODSThe Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events.Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval CI: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001).RESULTSAmong the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval CI: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001).HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.CONCLUSIONHCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.
Background and Aim
It is currently unknown how hepatitis C virus (HCV) eradication with pegylated interferon and ribavirin (PR) therapy affects the incidence of new‐onset liver cirrhosis (LC) in ...patients without cirrhosis and the incidence of decompensated liver disease (DLD) or hepatocellular carcinoma (HCC) in patients with cirrhosis.
Methods
Taiwanese chronic hepatitis C cohort (T‐COACH) is a nationwide HCV registry cohort from 23 hospitals in Taiwan recruited between 2003 and 2015. This study enrolled 10 693 patients with chronic hepatitis C (CHC), linked to the Taiwan National Health Insurance Research Database, receiving PR therapy for at least 4 weeks for new‐onset LC and liver‐related complications (DLD or HCC).
Results
Of the 10 693 patients, 1372 (12.8%) patients had LC, and the mean age was 54.0 ± 11.4 years. The mean follow‐up duration was 4.38 ± 2.79 years, with overall 46 798 person‐years. The 10‐year cumulative incidence rates of new‐onset LC were 5.0% (95% confidence interval CI: 3.2–7.7) in patients without cirrhosis with a sustained virologic response (SVR) and 21.9% (95% CI: 13.4–32.4) in those without SVR (hazard ratio HR: 0.22, P < 0.001). The 10‐year cumulative incidence rates of liver‐related complications were 21.4% (95% CI: 11.1–37.2) in patients with cirrhosis with SVR and 47.0% (95% CI: 11.1–86.0) in those without SVR after adjustment for age, sex, and competing mortality (HR: 0.52, P < 0.001).
Conclusions
Hepatitis C virus eradication with PR therapy decreased the incidence of new‐onset LC in noncirrhotic patients and the incidence of liver‐related complications in cirrhotic patients with CHC.
Reprocessing of gastrointestinal (GI) endoscopes and accessories is an essential part of patient safety and quality control in GI endoscopy centers. However, current endoscopic reprocessing ...guidelines or procedures are not adequate to ensure patient-safe endoscopy. Approximately 5.4 % of the clinically used duodenoscopes remain contaminated with high-concern microorganisms. Thus, the Digestive Endoscopy Society of Taiwan (DEST) sets standards for the reprocessing of GI endoscopes and accessories in endoscopy centers. DEST organized a task force working group using the guideline-revision process. These guidelines contain principles and instructions of step-by-step for endoscope reprocessing. The updated guidelines were established after a thorough review of the existing global and local guidelines, systematic reviews, and health technology assessments of clinical effectiveness. This guideline aims to provide detailed recommendations for endoscope reprocessing to ensure adequate quality control in endoscopy centers.
Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. Its biweekly dosing schema has demonstrated tolerability and clinical efficacy for treating chronic hepatitis in previous ...clinical studies. This trial evaluates the pharmacokinetics of 400 μg ropeginterferon alfa-2b in patients with chronic hepatitis C virus (HCV) and provides the data to support the clinical utility of ropeginterferon alfa-2b at 400 μg.
Seventeen patients with chronic HCV genotype 2 were enrolled to receive a single injection of 400 μg ropeginterferon alfa-2b plus 14-day treatment of ribavirin. Pharmacokinetics, safety, and HCV RNA reduction/clearance were assessed.
Tmax was 154.003 h and T1/2 was 114.273 h. The Cmax was 29.823 ng mL−1. AUClast was 9364.292 h∗ng mL−1 and AUCinf was 11084.317 h∗ng mL−1. All adverse events were mild or moderate, and there were no serious adverse events. A 1000-fold reduction in the geometric mean of HCV RNA was observed 14 d after the single injection of ropeginterferon alfa-2b. Two patients achieved clearance of HCV RNA, and the other five patients had HCV RNA levels lower than 200 IU mL−1.
Ropeginterferon alfa-2b at 400 μg led to PK exposures associated with safety and notable clinical activity in patients with chronic HCV. This study suggests that ropeginterferon alfa-2b at 400 μg is an acceptable dosing regimen for treating chronic HCV and also provides supporting data for the clinical use of ropeginterferon alfa-2b at a higher starting dose for other indications.