A phase I study of TAK-659 and paclitaxel in patients with taxane-refractory advanced solid tumors.

BACKGROUND: Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a possible resistance mechanism. This phase I trial evaluated the safety and preliminary activity of the SYK inhibitor TAK-659 combined with paclitaxel in patients with advanced taxane-refractory solid tumors. PATIENTS AND METHODS: Patients with advanced solid tumors and prior progression on taxane-based therapy received intravenous infusion of paclitaxel on days 1, 8, and 15 plus oral TAK-659 daily in 28-day cycles. The dose-escalation phase included six cohorts treated at different dose levels; the dose-expansion phase included patients with ovarian cancer treated at the highest dose level. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Efficacy was evaluated using Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: Our study included 49 patients. Maximum tolerated dose was not reached, but higher rates of adverse events were observed at higher dose levels. There were no treatment-related deaths. The most common treatment-related adverse events of any grade were increased aspartate aminotransferase (n = 31; 63%), increased alanine aminotransferase (n = 26; 53%), decreased neutrophil count (n = 26; 53%), and decreased white blood cell count (n = 26; 53%). Most adverse events were either grade 1 or 2. In the 44 patients with evaluable disease, 12 (27%) had stable disease as the best overall response, including three patients with prolonged stable disease, and 4 patients (9%) achieved a partial response. CONCLUSIONS: The combination of paclitaxel and TAK-659 showed preliminary activity possibly overcoming resistance to taxane-based therapy as well as a tolerable safety profile in patients with advanced solid tumors.

[Study on the application of self-fixing and self-detachable drainage stent in pancreaticojejunostomy].

Objectives: To evaluate the efficacy and safety of the self-fixing and self-detachable drainage stent in pancreaticojejunostomy and to provide supportive data for the follow clinical trials. Methods: This is an experimental research in animals which completed from February 2022 to September 2022. A self-fixing and self-detachable pancreaticojejunostomy drainage stent was designed for Hong's pancreaticojejunostomy technique based on the theory of "fistula healing" in pancreaticojejunostomy. Ten biocompatibility tests were completed in vitro before this study. Twenty-five Bama minipigs were selected and double-ligated in the neck of the pancreas to dilate the distal main pancreatic duct. Twenty-three of them were successfully modelled and divided into three groups by a stratified random method: pancreaticojejunostomy drainage stent group (referred to as stent group) with 11 pigs, pancreatic duct to jejunal mucosa anastomosis group (referred to as manual suture group) with 8 pigs, sham operation group with 4 pigs. The anastomic time,amylase content in postoperative abdominal drainage fluid and the tolerable pressure value of pancreaticojejunostomy were compared between the stent group and the manual suture group. An abdominal X-ray fluoroscopy examination was adopted to detect the detach time of the stent. A postoperative pathological examination was performed to verify the healing time,the type of treatment and the stricture rate of pancreaticojejunostomy. Quantitative data was analyzed by independent sample t-test. The classified data were analyzed by Fisher's exact test. Results: There were no significant differences in the diameter of the pancreatic duct and pancreatic texture,the time of pancreaticojejunostomy,the amylase content in postoperative peritoneal drainage fluid,and the tolerable pressure value of the pancreaticojejunostomy between the stent group and the manual suture group(all P>0.05). Abdominal X-ray fluoroscopy showed that the stents gradually detached and were removed from the body 21 days after operation,and all stents were detached in the follow 3 months after operation. Pancreaticojejunostomy healed 7 days after operation based on fistula formation in the stent group,and 14 days in the manual suture group. The incidence of anastomotic stricture within 35 days after operation was 2/8 in the stent group and 6/8 in the manual suture group (Fisher's exact test: P=0.132). Conclusion: The stent method is safer and simpler than the manual suture method in pancreaticojejunostomy of Bama minipigs, with shorter anastomotic healing time and lower stricture rate.

Ultrahigh energy storage in high-entropy ceramic capacitors with polymorphic relaxor phase.

Ultrahigh-power-density multilayer ceramic capacitors (MLCCs) are critical components in electrical and electronic systems. However, the realization of a high energy density combined with a high efficiency is a major challenge for practical applications. We propose a high-entropy design in barium titanate (BaTiO3)-based lead-free MLCCs with polymorphic relaxor phase. This strategy effectively minimizes hysteresis loss by lowering the domain-switching barriers and enhances the breakdown strength by the high atomic disorder with lattice distortion and grain refining. Benefiting from the synergistic effects, we achieved a high energy density of 20.8 joules per cubic centimeter with an ultrahigh efficiency of 97.5% in the MLCCs. This approach should be universally applicable to designing high-performance dielectrics for energy storage and other related functionalities.

Starting position during colonoscopy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Traditional teaching has been to place patients in the left lateral decubitus starting position for colonoscopies. Recent randomized controlled trials (RCTs) have compared left lateral decubitus starting position to other approaches. The aim of this systematic review and meta-analysis was to compare different starting positions for colonoscopies and their effect on cecal intubation. METHODS: MEDLINE, Embase, and CENTRAL were searched from inception to July 2023. Articles were eligible for inclusion if they were RCTs comparing at least two different starting positions for adults undergoing colonoscopy. The main outcome was cecal intubation time. Meta-analysis used an inverse variance random effects model. Risk of bias was assessed with the Cochrane Tool for RCTs 2.0. RESULTS: After screening 1523 citations, 14 RCTs were included. Four studies compared left lateral decubitus to right lateral decubitus, four studies compared left lateral decubitus to left lateral tilt-down, three studies compared left lateral decubitus to prone, and three studies compared left lateral decubitus to supine. There were no statistically significant differences in cecal intubation time in seconds across all comparisons: left lateral decubitus vs. right lateral decubitus (MD 14.9, 95% CI - 111.8 to 141.6, p = 0.82, I2 = 85%); left lateral decubitus vs. left lateral tilt-down (MD - 31.3, 95% CI - 70.8 to 8.3, p = 0.12, I2 = 82%); left lateral decubitus vs. prone (MD 17.2, 95% CI - 174.9 to 209.4, p = 0.86, I2 = 94%); left lateral decubitus vs. supine (MD - 149.9, 95% CI - 443.6 to 143.9, p = 0.32, I2 = 89%). CONCLUSION: The starting position for colonoscopies likely does not influence cecal intubation time. This study was limited by heterogeneity.

[Advancements and controversies in conversion therapy for biliary tract malignant tumors with insufficient future liver remnant].

Due to the unique location and aggressive tumor biology,hilar cholangiocarcinoma,intrahepatic cholangiocarcinoma,and gallbladder cancer often present with obstructive jaundice and require extensive liver resection,also exhibit high rates of recurrence and metastasis after radical excision. Therefore,surgeons should make treatment decisions based on the biliary anatomy of patients and the biological characteristics of tumors as it significantly affects patient's prognosis. Treatment strategy should be made to ensure the successful implementation of radical resection for biliary tract malignant tumors while maximizing the survival benefits of patients. Firstly,conversion of liver function by relieving jaundice technology and conversion of tumor biological characteristics through systematic therapy,followed by the conversion of future liver remnant. Currently,there are still controversies surrounding indications,methods,standards of relieving jaundice,and treatment plans,cycles,evaluation of therapeutic effects for systematic conversion therapy,and the standards and techniques of conversion therapy for future liver remnant.This article discusses these issues through literature analysis and the author's experience in the hope of resonating with colleagues.

The modified frailty index predicts postoperative morbidity in elective hernia repair patients: analysis of the national inpatient sample 2015-2019.

PURPOSE: Frailty has shown promise in predicting postoperative morbidity and mortality following hernia surgery. This study aims to evaluate the predictive capacity of the 11-item modified frailty index (mFI) in estimating postoperative outcomes following elective hernia surgery using the National Inpatient Sample (NIS) database. METHODS: A retrospective analysis of the NIS from 2015 to 2019 was performed including adult patients who underwent elective hernia repair. The mFI was used to stratify patients as either frail (mFI ≥ 0.27) or robust (mFI < 0.27). The primary outcomes were in-hospital postoperative morbidity and mortality. The secondary outcomes were system-specific morbidity, length of stay (LOS), total in-hospital healthcare cost, and discharge disposition. Univariable and multivariable regressions were utilized. RESULTS: In total, 14,125 robust patients and 1704 frail patients were included. Frailty was associated with an increased age (mean age 66.4 years vs. 52.6 years, p < 0.001) and prevalence of ventral hernias (51.9% vs. 44.4%, p < 0.001). Adjusted analyses demonstrated that frail patients had increased in-hospital mortality (adjusted odds ratio (aOR) 3.89, 95% CI 1.50, 10.11, p = 0.005), postoperative overall morbidity (aOR 1.98, 95% CI 1.72, 2.29, p < 0.001), postoperative LOS (adjusted mean difference (aMD) 0.78 days, 95% CI 0.51, 1.06, p < 0.001), total in-hospital healthcare costs (aMD $7562 95% CI 3292, 11,832, p = 0.001), and were less likely to be discharged home (aOR 0.61, 95% CI 0.53, 0.69, p < 0.001). CONCLUSION: The mFI may be a reliable predictor of postoperative morbidity and mortality in elective hernia surgery. Utilizing this tool can aid in patient education and identifying high-risk patients who may benefit from tailored prehabilitation.

Prognostic value of cardiac magnetic resonance imaging feature tracking technology in patients with light chain amyloidosis.

AIM: To undertake a meta-analysis of the prognostic value of cardiac magnetic resonance imaging feature tracking (CMR-FT) in patients with light-chain cardiac amyloidosis (LCA). MATERIALS AND METHODS: A systematic search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library. All analyses were conducted using RevMan 5.3 software. RESULTS: Eight studies were included with 663 patients. For the left ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired global circumferential (GCS), radial (GRS) and longitudinal (GLS) strain in survivors of LCA (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.09-1.25; 0.95, 0.93-0.96; 1.12, 1.05-1.20, all p<0.001). For ejection fraction (EF) and mass index, surviving patients had higher EFs and mass index (OR 0.96, 95% CI 0.96-0.97; 1.01, 1.01-1.02). For the right ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired GLS and GRS in survivors of LCA (OR 1.11, 95% CI 1.08-1.15; 0.93, 0.90-0.96, all p<0.001). Surviving patients had higher EFs (OR 0.97, 95% CI 0.96-0.98, p<0.001). Upon removing the studies one by one, there was no significant change in the results of the study. Both analyses showed no apparent publication deviation on funnel plots. CONCLUSION: Parameters derived from CMR-FT technology are promising new predictors for LCA, and are easily available and reliable. Patients with poor myocardial deformability are at highest risk of death.

Evaluation of Selected Markers in Kidneys of Cynomolgus Monkey (Macaca fascicularis) with Induced Diabetes during Renal Ischemia-reperfusion Injury.

We previously reported that induced type 1 diabetes mellitus (DM) increases the susceptibility of acute kidney injury in- duced by ischemia-reperfusion injury (IRI) in cynomolgus monkeys. In this follow-up study, we compared the expression of selected markers in the renal tissues of monkeys subjected to bilateral renal IRI with and without diabetes. All tissues were obtained from the original study. Renal biopsies were obtained before and 24 and 48 h after ischemia and were examined for expression of KI-67 (tubular proliferation), Na+ /K+ ATPase (sodium-potassium pump), TNF-α(tumor necrosis factor-α, inflammation), CD31 (microvessels), CD3 (T-cells), 2 fibrotic markers (fibroblast specific protein-1, FSP-1;α-smooth muscle actin,α -SMA), and cleaved caspase 3 (apoptosis). Generally, the expression of these markers differed in monkeys with and without DM. As compared with non-DM monkeys, DM monkeys had more cells that expressed KI-67 during progression of acute kidney injury (AKI). Na+ /K+ ATPase expression was clearly present at baseline in the basolateral tubular areas only in the non-DM monkeys. At 48 h, its expression in the basolateral area was not visible in DM monkeys, but was still present in intercellular junctions of non-DM monkeys. The expression of TNF-αwas higher in DM before and 48 h after ischemia. Before and 24 h after ischemia, the number of CD31-positive capillaries was not different between 2 groups, although more collapsed vessels were found at in DM at 24 h. At 48 h, the number of capillaries was less in DM compared with those from non-DM animals. DM monkeys had more interstitial CD3-positive cells than did non-DM monkeys at 24 and 48 h after ischemia. Finally, FSP-1-stained cells were more abundant in DM than non-DM at 24 and 48 h. Our results show that DM aggravates the recovery of renal ischemia/reperfusion injury by affecting tubular proliferation, capillary density, T cell infil- tration and by altering protein and mRNA expression of various genes involved in ion channel, inflammation, and fibrotic change. The results from this observational study demonstrate that DM aggravates the recovery of renal ischemia/reperfusion injury by affecting multiple events including tubular necrosis, proliferation, function, inflammation and by inducing capillary rarefaction in cynomolgus monkeys.

Cutting seton for the treatment of cryptoglandular fistula-in-ano: a systematic review and meta-analysis.

BACKGROUND: The use of cutting seton (CS) for the management of cryptoglandular fistula-in-ano has remained controversial because of reports of fecal incontinence, postoperative pain, and extended healing time. The aim of this review was to provide the first synthesis of studies investigating the use of CS for the treatment of cryptoglandular fistula-in-ano. METHODS: MEDLINE, Embase, and CENTRAL were searched up to October 2022. Randomized controlled trials and observational studies comparing CS with alternative interventions were included, along with single-arm studies evaluating CS alone. The primary outcome was fistula-in-ano recurrence, and secondary outcomes included incontinence, healing time, proportion with complete healing, and postoperative pain. Inverse variance random-effects meta-analyses were used to pool effect estimates. RESULTS: After screening 661 citations, 29 studies were included. Overall, 1513 patients undergoing CS (18.8% female, mean age: 43.1 years) were included. Patients with CS had a 6% (95% CI: 3-12%) risk of recurrence and a 16% (95% CI: 5-38%) risk of incontinence at 6 months. CS patients had an average healing time of 14.6 weeks (95% CI: 10-19 weeks) with 73% (95% CI: 48-89%) of patients achieving complete healing at 6 months postoperatively. There was no difference in recurrence between CS and fistulotomy, advancement flap, two-stage seton fistulotomy, or draining seton. CONCLUSIONS: Overall, this analysis shows that CS has comparable recurrence and incontinence rates to other modalities. However, this may be at the expense of more postoperative pain and extended healing time. Further comparative studies between CS and other modalities are warranted.

[Progress in surgical treatment of hepatocellular carcinoma with tumor thrombus in the inferior vena cava].

Hepatocellular carcinoma(HCC) is one of the most common malignancies of the digestive system,which is prone to be associated with microvascular or macrovascular invasion. Among them,HCC with inferior vena cava tumor thrombus(IVCTT) or right atrium tumor thrombus(RATT) is rare and has a poor prognosis. However,surgical treatment of HCC with IVCTT and (or) RATT is rarely reported and summarized. The review described the classification of HCC tumor thrombus with IVCTT and (or) RATT, summarized the progress of surgical approaches and surgical operations,and introduced a case of thrombectomy after pushing from the outer surface of the atrium,rendering the RATT to the inferior vena cava under non-cardiopulmonary bypass. The review also proposed the prospective treatments for HCC with IVCTT or RATT,providing clinical guidance to hepatobiliary surgeons.

[The clinical value of radical resection of retroperitoneal lipo-lymphatic layer for pancreatic head cancer].

Objective: To investigate the clinical value of the novel approach,radical resection of the retroperitoneal lipo-lymphatic layer (RRRLLL),in the surgical treatment of resectable pancreatic head cancer. Methods: Between June 2020 and June 2022,a total of 221 patients with pancreatic head cancer underwent surgical treatment using the RRRLLL approach(RRRLLL group),while 107 patients received traditional surgical treatment(traditional group) in five high-volume pancreatic centers in China. Data from surgical technique and clinical perioperative outcomes,including lymph node harvested,surgical time,and complications,were analyzed. The RRRLLL group consisted of 144 males and 77 females with an age of (67.5±9.0) years(range:41.3 to 81.1 years). The traditional group included 71 males and 36 females,with an age of (66.3±8.1) years(range:45.1 to 79.2 years). Statistical analysis was performed using the K-S test,Z test,or χ2 test. Results: Pancreaticoduodenectomy was performed successfully in all patients,achieving R0 resection. RRRLLL group surgery required mobilization of retroperitoneal adipose and lymphatic tissues starting from the right edge of the inferior vena cava and extending to the left side,up to the superior mesenteric artery,down to the inferior mesenteric artery,and left to the left side of the aorta,including the perineural and lymphatic tissues around the superior mesenteric artery and the sheath of the mesenteric artery. However,the traditional group did not include the areas mentioned above in the scope of clearance. There were no statistically significant differences between the RRRLLL group and the traditional group in terms of age,sex,tumor size,T stage,and vascular invasion (all P>0.05). However,the number of lymph nodes harvested in the RRRLLL group was significantly higher at 28.7±9.0 (range: 18 to 39) compared to 18.2±8.0 (range: 12 to 21) in the traditional group (Z=-10.691,P<0.05). There were no statistically significant differences in the number of positive lymph nodes,N staging,and postoperative complications between the two groups. Conclusion: The RRRLLL approach improved lymph node dissection compared to the traditional approach,potentially leading to reduced recurrence rates.

Optimal ropivacaine concentration for ultrasound-guided erector spinae plane block in patients who underwent video-assisted thoracoscopic lobectomy surgery.

Background: An ultrasound-guided erector spinae plane block (ESPB) has emerged as an effective way to control postoperative pain and may be a good alternative way to an epidural block. However, relevant research on the appropriate concentration of local anesthetics for an ESPB remains scarce. Aims: This study aimed to investigate the optimal concentration of ropivacaine for an ESPB in patients undergoing video-assisted thoracoscopic surgery (VATS). Methods: A total of 68 patients who underwent a VATS lobectomy were enrolled. An ipsilateral ultrasound-guided ESPB was performed with three different ropivacaine concentrations as a local anesthetic: 0.189% (G1), 0.375% (G2), and 0.556% (G3). The total amount of perioperative remifentanil administered, patient-controlled analgesia (PCA) applied, and rescue drugs for postoperative analgesia during the 24 h after surgery were acquired, and numeric rating scale (NRS) scores were obtained. Results: The total amount of intraoperative remifentanil administered was 7.20 ± 3.04 mcg/kg, 5.32 ± 2.70 mcg/kg, and 4.60 ± 1.75 in the G1, G2, and G3 groups, respectively. G2 and G3 had significantly lower amounts of remifentanil administered than the G1 group (P = 0.02 vs. G2; P = 0.003 vs. G3). The G3 group needed more inotropes than the G1 and G2 groups in the perioperative period (P = 0.045). The NRS scores, PCA, and rescue drug were not significantly different in the three groups. Conclusion: The optimal concentration of ropivacaine recommended for an ESPB was 0.375%, which was effective in controlling pain and reducing the intraoperative opioid requirements with minimal adverse reactions such as hypotension.

[Application of membrane anatomy in hepatopancreatobiliary and splenic surgery].

Understanding of a variety of membranous structures throughout the body,such as the fascia,the serous membrane,is of great importance to surgeons. This is especially valuable in abdominal surgery. With the rise of membrane theory in recent years,membrane anatomy has been widely recognized in the treatment of abdominal tumors,especially of gastrointestinal tumors. In clinical practice. The appropriate choice of intramembranous or extramembranous anatomy is appropriate to achieve precision surgery. Based on the current research results,this article described the application of membrane anatomy in the field of hepatobiliary surgery,pancreatic surgery,and splenic surgery,with the aim of blazed the path from modest beginnings.

Impact of frailty on hiatal hernia repair: a nationwide analysis of in-hospital clinical and healthcare utilization outcomes.

Previous studies recommend a watch-and-wait approach to paraesophageal hernia (PEH) repair due to an increased risk for mortality. While contemporary studies suggest that elective surgery is safe and effective, many patients presenting with PEH are elderly. Therefore, we assessed the impact of frailty on in-hospital outcomes and healthcare utilization among patients receiving PEH repair. This retrospective population-based cohort study assessed patients from the National Inpatient Sample database who received PEH repair between October 2015 to December 2019. Demographic and perioperative data were gathered, and frailty was measured using the 11-item modified frailty index. The outcomes measured were in-hospital mortality, complications, discharge disposition, and healthcare utilization. Overall, 10,716 patients receiving PEH repair were identified, including 1442 frail patients. Frail patients were less often female and were more often in the lowest income quartile compared to robust patients. Frail patients were at greater odds for in-hospital mortality [odds ratio (OR) 2.83 (95% CI 1.65-4.83); P < 0.001], postoperative ICU admissions [OR 2.07 (95% CI 1.55-2.78); P < 0.001], any complications [OR 2.18 (95% CI 1.55-2.78); P < 0.001], hospital length of stay [mean difference (MD) 1.75 days (95% CI 1.30-2.210; P < 0.001], and total admission costs [MD $5631.65 (95% CI $3300.06-$7.963.24); P < 0.001] relative to their robust patients. While PEH repair in elderly patients is safe and effective, frail patients have an increased rate of in-hospital mortality, postoperative ICU admissions, complications, and total admission costs. Clinicians should consider patient frailty when identifying the most appropriate surgical candidates for PEH repair.

The Efficacy of At-home, In-office, and Combined Bleaching Regimens: A Randomized Controlled Clinical Trial.

OBJECTIVE: The aim of this study was to compare the clinical efficacy of at-home, in-office, and combined bleaching regimens. METHODS: Forty-eight participants were recruited and randomly divided into four groups based on the bleaching regimen (n=12) as follows: 1) at-home bleaching using 10% carbamide peroxide (Opalescence PF 10%, Ultradent) for 14 days (HB); 2) two sessions of in-office bleaching using 40% hydrogen peroxide (Opalescence BOOST PF 40%, Ultradent) with a one-week interval (OB); 3) one session of in-office bleaching followed by at-home bleaching for seven days (OHB); and 4) at-home bleaching for seven days followed by one session of in-office bleaching (HOB). Tooth color was measured using a spectrophotometer (Easyshade, Vita ZahnFabrik) at baseline (T0), day 8 (T1), day 15 (T2), and day 43 (T3, four weeks after the end of the bleaching treatment). The color data were calculated using the CIEDE2000 (ΔE00) and whiteness index for dentistry (WID) formulas. Tooth sensitivity (TS) was recorded using a visual analogue scale (VAS) for 16 days. Data were analyzed by one-way analysis of variance (ANOVA) and the Wilcoxon signed-rank test (α=0.05). RESULTS: All bleaching regimens resulted in a significant increase in WID values (all p<0.05), while no significant differences in WID and ΔWID values were found among the different groups at each time point (all p>0.05). Significant differences in ΔE00 values were observed between T1 and T3 for all groups (all p<0.05), while no significant differences in ΔE00 values were found among the different groups at any time point (all p>0.05). Significantly lower TS values were observed in the HB group than in the OB and HOB groups (p=0.006 and p=0.001, respectively). CONCLUSIONS: All bleaching regimens resulted in great color improvement, and different regimens led to similar color changes at any of the evaluation time points. The sequence of treatments applying in-office bleaching or at-home bleaching did not affect the bleaching efficacy. The in-office bleaching and combined bleaching regimens yielded a higher intensity of TS than did at-home bleaching.

Differences in in-hospital outcomes and healthcare utilization for laparoscopic versus open approach for emergency inguinal hernia repair: a nationwide analysis.

PURPOSE: There has been a growing debate of whether laparoscopic or open surgical techniques are superior for inguinal hernia repair. For incarcerated and strangulated inguinal hernias, the laparoscopic approach remains controversial. This study aims to be the first nationwide analysis to compare clinical and healthcare utilization outcomes between laparoscopic and open inguinal hernia repair in an emergency setting. METHODS: A retrospective analysis of the National Inpatient Sample was performed. All patients who underwent laparoscopic inguinal hernia repair (LIHR) and open inguinal hernia repair (OIHR) between October 2015 and December 2019 were included. The primary outcome was mortality, and secondary outcomes include post-operative complications, ICU admission, length of stay (LOS), and total admission cost. Two approaches were compared using univariate and multivariate logistic and linear regression. RESULTS: Between the years 2015 and 2019, 17,205 patients were included. Among these, 213 patients underwent LIHR and 16,992 underwent OIHR. No difference was observed between laparoscopic and open repair for mortality (odds ratio [OR] 0.80, 95% CI [0.25, 2.61], p = 0.714). Additionally, there was no significant difference between groups for post-operative ICU admission (OR 1.11, 95% CI [0.74, 1.67], p = 0.614), post-operative complications (OR 1.09, 95% CI [0.76, 1.56], p = 0.647), LOS (mean difference [MD]: -0.02 days, 95% CI [- 0.56, 0.52], p = 0.934), or total admission cost (MD: $3,028.29, 95% CI [$- 110.94, $6167.53], p = 0.059). CONCLUSION: Laparoscopic inguinal hernia repair is comparable to the open inguinal hernia repair with respect to low rates of morbidity, mortality as well as healthcare resource utilization.

High-fidelity dendritic sodium spike generation in human layer 2/3 neocortical pyramidal neurons.

Dendritic spikes function as cardinal components of rodent neocortical circuit computations. Recently, the biophysical properties of human pyramidal neurons (PNs) have been reported to be divergent, raising the question of whether dendritic spikes have homologous roles in the human neocortex. To directly address this, we made electrical recordings from the soma and apical dendrites of human and rat layer 2/3 PNs of the temporal cortex. In both species, dendritic excitatory input led to the initiation of sodium-channel-mediated dendritic spikes. Dendritic sodium spikes could be generated across a wide input range, exhibited a similar frequency range of activation, and forward-propagated with high-fidelity to implement stereotyped computations in human and rat PNs. However, the physical expansion and complexification of the apical dendritic trees of human PNs allowed the enriched expression of dendritic spike generation. The computational capacity of human PNs is therefore enhanced by the widespread implementation of a conserved dendritic integration mechanism.

[Ten-year retrospect of ALPPS in the treatment of hepatocellular carcinoma:an eternal concept with cautious technologic choice].

Clinical practice using associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) or its modified procedures in treatment of primary hepatocellular carcinoma(HCC) with insufficient future liver remnant(FLR) in the past 10 years has failed to meet our expectations both in achieving decreased perioperative complications and mortality.The efficacy of ALPPS in improving long-term survival outcome of HCC still remains poor.Due to the trauma of two surgery within a short period,and patients with inadequate FLR are all diagnosed at advanced disease stages,ALPPS can only achieve surgical rather than biological tumor-curability.Previous studies have demonstrated comparable 5-year survival rates between early and advanced stages of HCC who underwent regional treatments.Therefore,tumor biological conversion is the key strategy prior to liver remnant volume conversion in improving treatment outcomes for HCC patients with insufficient FLR.Target therapy,immunotherapy together with locally treatment were expected to improve the conversion efficacy.Looking back at the development of ALPPS for the last decade,the rapid proliferation of FLR should be passed on,while the technology costs high risks and result in poor long-term outcome must be cautiously selected.

Epidemiology of resistance of carbapenemase-producing Klebsiella pneumoniae to ceftazidime-avibactam in a Chinese hospital.

AIMS: Klebsiella pneumoniae has been reported to develop increased antibiotic resistance. Ceftazidime-avibactam (CZA) is a novel antibiotic with activity against serine-lactamase. Here, we investigated the sensitivity of carbapenem-resistant K. pneumoniae (CRKP) to CZA and the mechanisms of drug resistance in our hospital. METHODS AND RESULTS: Patient characteristics were obtained from medical records. K. pneumoniae and its antibiotic susceptibility were determined using the Vitek-2 Compact instrument. The antibiotic resistance genes KPC, NDM, OXA-48, VIM, IMP, CIM, SPM, TMB, SMB, SIM, AIM and DIM were detected using real-time PCR. Multilocus sequence typing was used for genetic RELATEDNESS analysis. In total, 121 CRKP strains were isolated from patients in the intensive care unit (51·2%), senior ward (12·4%) and neurosurgery department (10%). With an average age of 72·5 years, most patients were in care for respiratory (34·7%), brain (20·7%), digestive tract (13·2%) and cardiovascular (8·3%) diseases. Specimens were predominantly obtained from sputum (39·67%), urine (29·75%) and blood (6·61%). CONCLUSION: Of 23 CZA-resistant CRKP strains (19·01%), ST11 being the most common at 56·52%, 11 NDM-1-positive (47·83%) and four NDM-5-positive (17·39%) strains were detected. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study indicates that CZA resistance occurs in ~19·01% CRKP strains and that blaNDM-1 and blaNDM-5 might be critical for resistance.

Beyond epidermal growth factor receptor: MET amplification as a general resistance driver to targeted therapy in oncogene-driven non-small-cell lung cancer.

The rapidly changing treatment paradigm for patients with metastatic oncogene-driven lung cancer continues to evolve, and consequently our understanding of the landscape of resistance must also advance. MET amplification is an established and frequent driver of resistance in EGFR-mutant non-small-cell lung cancer (NSCLC). Recently, the combination of MET proto-oncogene (MET) and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has shown promise in overcoming this molecularly defined resistance in clinical trials, and this combination strategy is being pursued in ongoing trials. Emerging data also demonstrate MET amplification as a resistance driver to TKI-treated ALK-, RET-, and ROS-1-fusion NSCLC, consistently at the range of 15%, while the resistance profiling data are maturing for other molecular targets. In this review, we discuss MET amplification as a driver of acquired resistance in well-defined molecular subsets of NSCLC, explore the biology behind this mechanism of resistance, and summarize the recently published clinical data, including the proposed combination strategies in the clinic achieving success in overcoming acquired MET amplification-dependent resistance.