Intraocular pressure variation during colorectal laparoscopic surgery: standard pneumoperitoneum leads to reversible elevation in intraocular pressure

Background

The potential effects of laparoscopic surgery on intra- and postoperative intraocular pressure (IOP) are not completely understood. Although prior studies have reported that pneumoperitoneum may increase IOP, it is not clear whether this increase is related to the effects of pneumoperitoneum or to the patient’s position, such as the Trendelenburg position. This study aimed to evaluate the potential fluctuations of IOP during colorectal laparoscopic surgery in two groups of patients: those with and those without Trendelenburg positioning.

Methods

For this prospective study 45- to 85-year-old patients undergoing laparoscopic colorectal surgery were enrolled after a thorough ophthalmologic assessment. The study protocol included measurement of IOP at eight different time points (before, during, and after surgery) using a contact tonometer in both eyes.

Results

The study enrolled 29 patients: 17 (58.6 %) with Trendelenburg position placement during surgery and 12 (41.4 %) without Trendelenburg positioning. The two groups did not differ in terms of gender, age, body mass index (BMI), American Society of Anesthesiology (ASA) class, or operative time. In all the patients, pneumoperitoneum induction led to a mild rise in IOP, averaging 4.1 mmHg. The patients with Trendelenburg positioning showed a greater increase than the patients without it (5.05 vs 4.23 mmHg at 45 min; p = 0.179), but IOP evaluation 48 h after surgery showed no substantial differences between the two groups. Among the 29 patients, 17 (58.6 %) showed an increase in IOP of 5 mmHg or more during surgery. A greater percentage of the patients who underwent Trendelenburg positioning showed an IOP increase of 5 mmHg or more (76.5 vs 33.3 %; p = 0.020). At the multivariate analysis, no potential predictors of increased IOP during surgery was identified.

Conclusions

Standard pneumoperitoneum (≤14 mmHg) led to mild and reversible IOP increases. A trend was observed toward a greater IOP increase in patients with Trendelenburg positioning. Thus, the patient’s position during surgery may represent a stronger risk factor for IOP increase than pneumoperitoneum-related intraabdominal pressure.     

Cytoreduction and HIPEC in The Netherlands: Nationwide Long-term Outcome Following the Dutch Protocol

Purpose

This nationwide study evaluated results of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis of colorectal origin in the Netherlands following a national protocol.

Methods

In a multi-institutional study prospective databases of patients with peritoneal carcinomatosis (PC) from colorectal cancer and pseudomyxoma peritonei (PMP) treated according to the Dutch HIPEC protocol, a uniform approach for the CRS and HIPEC treatment, were reviewed. Primary end point was overall survival and secondary end points were surgical outcome and progression-free survival.

Results

Nine-hundred sixty patients were included; 660 patients (69 %) were affected by PC of colorectal carcinoma and the remaining suffered from PMP (31 %). In 767 procedures (80 %), macroscopic complete cytoreduction was achieved. Three-hundred and thirty one patients had grade III–V complications (34 %). Thirty-two patients died perioperatively (3 %). Median length of hospital stay was 16 days (range 0–166 days). Median follow-up period was 41 months (95 % confidence interval (CI), 36–46 months). Median progression-free survival was 15 months (95 % CI 13–17 months) for CRC patients and 53 months (95 % CI 40–66 months) for PMP patients. Overall median survival was 33 (95 % CI 28–38 months) months for CRC patients and 130 months (95 % CI 98–162 months) for PMP patients. Three- and five-year survival rates were 46 and 31 % respectively in case of CRC patients and 77 and 65 % respectively in case of PMP patients.

Conclusions

The results underline the safety and efficacy of cytoreduction and HIPEC for PC from CRC and PMP. It is assumed the uniform Dutch HIPEC protocol was beneficial.     

Phosphorylation of rat aquaporin‐4 at Ser111 is not required for channel gating

Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain‐blood interface. AQP4 has been described as an important entry and exit site for water during formation of brain edema and regulation of AQP4 is therefore of therapeutic interest. Phosphorylation of some aquaporins has been proposed to regulate their water permeability via gating of the channel itself. Protein kinase (PK)‐dependent phosphorylation of Ser¹¹¹ has been reported to increase the water permeability of AQP4 expressed in an astrocytic cell line. This possibility was, however, questioned based on the crystal structure of the human AQP4. Our study aimed to resolve if Ser¹¹¹ was indeed a site involved in phosphorylation‐mediated gating of AQP4. The water permeability of AQP4‐expressing Xenopus oocytes was not altered by a range of activators and inhibitors of PKG and PKA. Mutation of Ser¹¹¹ to alanine or aspartate (to prevent or mimic phosphorylation) did not change the water permeability of AQP4. PKG activation had no effect on the water permeability of AQP4 in primary cultures of rat astrocytes. Molecular dynamics simulations of a phosphorylation of AQP4.Ser¹¹¹ recorded no phosphorylation‐induced change in water permeability. A phospho‐specific antibody, exclusively recognizing AQP4 when phosphorylated on Ser¹¹¹, failed to detect phosphorylation in cell lysate of rat brain stimulated by conditions proposed to induce phosphorylation of this residue. Thus, our data indicate a lack of phosphorylation of Ser¹¹¹ and of phosphorylation‐dependent gating of AQP4.     

Defining in vivo dose-response curves for kidney DNA adduct formation of aristolochic acid I in rat,mouse and human by an in vitro and physiologically based kinetic modeling approach

Aristolochic acid I (AAI) is a well-known genotoxic kidney carcinogen. Metabolic conversion of AAI into the DNA-reactive aristolactam-nitrenium ion is involved in the mode of action of tumor formation. This study aims to predict in vivo AAI-DNA adduct formation in the kidney of rat, mouse and human by translating the in vitro concentration-response curves for AAI-DNA adduct formation to the in vivo situation using physiologically based kinetic (PBK) modeling-based reverse dosimetry. DNA adduct formation in kidney proximal tubular LLC-PK1 cells exposed to AAI was quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry. Subsequently, the in vitro concentration-response curves were converted to predicted in vivo dose-response curves in rat, mouse and human kidney using PBK models. Results obtained revealed a dose-dependent increase in AAI-DNA adduct formation in the rat, mouse and human kidney and the predicted DNA adduct levels were generally within an order of magnitude compared with values reported in the literature. It is concluded that the combined in vitro PBK modeling approach provides a novel way to define in vivo dose-response curves for kidney DNA adduct formation in rat, mouse and human and contributes to the reduction, refinement and replacement of animal testing.     

Postural adjustments and reaching in 4- and 6-month-old infants: an EMG and kinematical study

Adequate postural control is a prerequisite for daily activities such as reaching for an object. However, knowledge on the relationship between postural adjustments and the quality of reaching movements during human ontogeny is scarce. Therefore we evaluated the development of the relationship between the kinematic features of reaching movements and the accompanying postural adjustments in young infants. Twelve typically developing (TD) infants were assessed twice, i.e. at 4 and 6 months of age, in supine and supported sitting position. Reaching was elicited by presenting toys in the midline at an arm-length distance while simultaneously surface EMG-activity was recorded from multiple arm-, neck-, trunk- and leg muscles. Concurrently kinematics of reaching were recorded with an ELITE system; kinematic analysis was restricted to the behaviour of so-called movement units, which are sub movements of reaching determined with the help of peaks in the velocity profile of the hand, maximum movement velocity and movement duration. A computer-algorithm determined significant phasic muscle activity. Activity in neck and trunk muscles (postural activity) was related to the onset of the prime mover, which was the arm muscle being activated first. The results indicated that about 50% of reaching movements in lying and sitting infants aged 4 and 6 months were accompanied by direction-specific postural adjustments. At 4 months variation dominated, but at 6 months a preference to recruit muscles in a top-down order (during sitting) and in the configuration of the complete pattern, i.e. the pattern in which all dorsal neck- and trunk muscles are activated in concert, (both conditions) emerged. Interestingly, the postural characteristics such as the presence of direction-specificity, recruitment of the complete pattern and top-down recruitment, were related to how successful the reaching was and the kinematics of reaching. It was concluded that the presence of direction-specific activity is not a prerequisite for the emergence of reaching movements. Nevertheless, already from 4 months onwards a better postural control is associated with a larger success and a better quality of reaching.     

Evaluation of Training Program for the Maternal and Child Health Workforce at Tulane University

Objectives Despite significant investments in Maternal and Child Health (MCH), the United States still lags behind other countries in key MCH indicators. A well-trained workforce is needed to improve MCH. The Division of MCH Workforce Development of HRSA’s Maternal and Child Health Bureau provides funding to schools of Public Health to support Centers of Excellence in MCH, which is focused on preparing the next generation of MCH leaders through specialized training and mentorship. One such center, the Tulane Center of Excellence in MCH (CEMCH), is housed at the Tulane University School of Public Health and Tropical Medicine. This study evaluated the perceived effectiveness and acceptability of the CEMCH leadership training program. Methods A mixed-methods approach was used, consisting of semi-structured interviews and quantitative surveys which were analyzed through inductive methods based in grounded theory and non-parametric methods respectively. Results Results indicated an overall high level of program satisfaction by all stakeholders. Mentorship and personal attention emerged as an important benefit for both former and current Scholars. The opportunity to gain real-world understanding of MCH work through program activities was an added benefit, although these activities also presented the most challenges. Community stakeholders generally did not view the program as providing immediate organizational benefit, but recognized the distal benefit of contributing to a well-trained MCH workforce. Conclusions for Practice These results will be used to inform other MCH training programs and strengthen Tulane’s CEMCH. A well-trained MCH workforce is essential to improving MCH, and high-quality training its foundation.