Major Increase in Incidence of Pediatric ACL Reconstructions From 2005 to 2021: A Study From the Norwegian Knee Ligament Register.

BACKGROUND: The incidence of pediatric and adolescent anterior cruciate ligament reconstruction (ACLR) is increasing in several countries. It is uncertain whether this trend applies to countries that traditionally prefer an initial nonoperative treatment approach whenever possible, like Norway. Nationwide, long-term patient-reported outcomes and revision rates after ACLR in the pediatric population are also lacking. PURPOSE: To determine the incidence of pediatric ACLR in Norway since 2005, as well as to detect trends in surgical details and describe patient-reported outcomes up to 10 years after ACLR. STUDY DESIGN: Descriptive cohort study. METHODS: This study is based on prospectively collected data on girls ≤14 years and boys ≤16 years, registered in the Norwegian Knee Ligament Register at the time of their primary ACLR, between 2005 and 2021. The main outcome was the incidence of ACLR, adjusted to the corresponding population numbers for each year. The time trend was analyzed by comparing the mean of the first and last 3-year period (2005-2007 and 2019-2021). Patient-reported outcomes were assessed using the Knee injury and Osteoarthritis Outcome Score preoperatively and at 2, 5, and 10 years postoperatively. RESULTS: A total of 1476 patients (1484 cases) were included, with a mean follow-up of 8.1 years (range, 1-17). The incidence of pediatric ACLRs per 100,000 population increased from 18 to 26, which corresponds to an increase of 40% for boys and 55% for girls. Concurrent meniscal procedures increased significantly from 45% to 62%, and the proportion of meniscal repairs increased from 19% to 43% when comparing the first and last time period. The mean Knee injury and Osteoarthritis Outcome Score values for the Sport and Recreation and Quality of Life subscales were between 72 and 75 at the 2-, 5- and 10-year follow-up. The 5-year revision rate was 9.9%. CONCLUSION: There was a major increase in incidence of pediatric ACLR in Norway during the study period. There was a shift in the approach to concomitant meniscal procedures from resection to repair, with more than a doubling of the proportion of meniscal repairs. Patient-reported outcomes revealed long-lasting reduced knee function.

Comparing the effects of continuous positive airway pressure via mask or helmet interface on oxygenation and pulmonary complications after major abdominal surgery: a randomized trial.

The risk of pulmonary complications is high after major abdominal surgery but may be reduced by prophylactic postoperative noninvasive ventilation using continuous positive airway pressure (CPAP). This study compared the effects of intermittent mask CPAP (ICPAP) and continuous helmet CPAP (HCPAP) on oxygenation and the risk of pulmonary complications following major abdominal surgery. Patients undergoing open abdominal aortic aneurysm repair or pancreaticoduodenectomy were randomized (1:1) to either postoperative ICPAP or HCPAP. Oxygenation was evaluated as the partial pressure of oxygen in arterial blood fraction of inspired oxygen ratio (PaO2/FIO2) at 6 h, 12 h, and 18 h postoperatively. Pulmonary complications were defined as X-ray verified pneumonia/atelectasis, clinical signs of pneumonia, or supplementary oxygen beyond postoperative day 3. Patient-reported comfort during CPAP treatment was also evaluated. In total, 96 patients (ICPAP, n = 48; HCPAP, n = 48) were included, and the type of surgical procedure were evenly distributed between the groups. Oxygenation did not differ between the groups by 6 h, 12 h, or 18 h postoperatively (p = 0.1, 0.08, and 0.67, respectively). Nor was there any difference in X-ray verified pneumonia/atelectasis (p = 0.40) or supplementary oxygen beyond postoperative day 3 (p = 0.53). Clinical signs of pneumonia tended to be more frequent in the ICPAP group (p = 0.06), yet the difference was not statistically significant. Comfort scores were similar in both groups (p = 0.43), although a sensation of claustrophobia during treatment was only experienced in the HCPAP group (11% vs. 0%, p = 0.03). Compared with ICPAP, using HCPAP was associated with similar oxygenation (i.e., PaO2/FIO2 ratio) and a similar risk of pulmonary complications. However, HCPAP treatment was associated with a higher sensation of claustrophobia.

Mid-regional plasma pro-atrial natriuretic peptide and stroke volume responsiveness for detecting deviations in central blood volume following major abdominal surgery.

BACKGROUND: A reduced central blood volume is reflected by a decrease in mid-regional plasma pro-atrial natriuretic peptide (MR-proANP), a stable precursor of ANP, and a volume deficit may also be assessed by the stroke volume (SV) response to head-down tilt (HDT). We determined plasma MR-proANP during major abdominal procedures and evaluated whether the patients were volume responsive by the end of the surgery, taking the fluid balance and the crystalloid/colloid ratio into account. METHODS: Patients undergoing pancreatic (n = 25), liver (n = 25), or gastroesophageal (n = 38) surgery were included prospectively. Plasma MR-proANP was determined before and after surgery, and the fluid response was assessed by the SV response to 10° HDT after the procedure. The fluid strategy was based mainly on lactated Ringer's solution for gastroesophageal procedures, while for pancreas and liver surgery, more human albumin 5% was administered. RESULTS: Plasma MR-proANP decreased for patients undergoing gastroesophageal surgery (-9% [95% CI -3.2 to -15.3], p = .004) and 10 patients were fluid responsive by the end of surgery (∆SV > 10% during HDT) with an administered crystalloid/colloid ratio of 3.3 (fluid balance +1389 ± 452 ml). Furthermore, plasma MR-proANP and fluid balance were correlated (r = .352 [95% CI 0.031-0.674], p < .001). In contrast, plasma MR-proANP did not change significantly during pancreatic and liver surgery during which the crystalloid/colloid ratio was 1.0 (fluid balance +385 ± 478 ml) and 1.9 (fluid balance +513 ± 381 ml), respectively. For these patients, there was no correlation between plasma MR-proANP and fluid balance, and no patient was fluid responsive. CONCLUSION: Plasma MR-proANP was reduced in fluid responsive patients by the end of surgery for the patients for whom the fluid strategy was based on more lactated Ringer's solution than human albumin 5%.

A semaphorin-plexin-Rasal1 signaling pathway inhibits gastrin expression and protects against peptic ulcers.

Peptic ulcer disease is a frequent clinical problem with potentially serious complications such as bleeding or perforation. A decisive factor in the pathogenesis of peptic ulcers is gastric acid, the secretion of which is controlled by the hormone gastrin released from gastric G cells. However, the molecular mechanisms regulating gastrin plasma concentrations are poorly understood. Here, we identified a semaphorin-plexin signaling pathway that operates in gastric G cells to inhibit gastrin expression on a transcriptional level, thereby limiting food-stimulated gastrin release and gastric acid secretion. Using a systematic siRNA screening approach combined with biochemical, cell biology, and in vivo mouse experiments, we found that the RasGAP protein Rasal1 is a central mediator of plexin signal transduction, which suppresses gastrin expression through inactivation of the small GTPase R-Ras. Moreover, we show that Rasal1 is pathophysiologically relevant for the pathogenesis of peptic ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs), a main risk factor of peptic ulcers in humans. Last, we show that application of recombinant semaphorin 4D alleviates peptic ulcer disease in mice in vivo, demonstrating that this signaling pathway can be harnessed pharmacologically. This study unravels a mode of G cell regulation that is functionally important in gastric homeostasis and disease.

A preliminary simulation-based qualitative study of healthcare students' experiences of interprofessional primary care scenarios.

BACKGROUND: Introducing interprofessional education (IPE) in healthcare curricula can prepare students for healthcare practices that have become increasingly complex. The use of simulation is promoted to support IPE. This study explores healthcare students' experiences of participating in common, sub-acute patient scenarios that routinely occur in clinical practice in primary care. More specifically, it looks at how sub-acute patient scenarios from primary care can help develop interprofessional collaborative competence. METHODS: Medical students (N = 10), master's students in advanced geriatric nursing (N = 8) and bachelor's students in nursing (N = 9) participated in the simulations. The students were in their last or second-to-last year of education. We conducted five semi-structured focus group interviews with the participants' directly after the simulation training to elicit experiences related to the scenarios, the simulation and interprofessional collaboration. The transcripts were analysed using systematic text condensation. To supplement the focus group interviews, the students also completed the interprofessional collaborative competency attainment survey (ICCAS), which measures the students' self-assessed interprofessional competence. RESULTS: Three main themes emerged from the analysis of the focus group interviews: realism, uncertainty and reflection. The students emphasised the importance of authentic and recognisable scenarios. They said the vague and unspecific patient symptoms created uncertainty in the situation, making it difficult to understand the patient's diagnosis. Despite that uncertainty, they described the experience as positive. Further, the students expressed that the simulation increased their confidence in interprofessional collaboration and prepared them for future work. The results from the ICCAS questionnaire showed that the students reported a subjective positive change in their interprofessional competence after participating in the scenarios. CONCLUSIONS: This study showed that simulation-based IPE with sub-acute primary care scenarios contributes to develop interprofessional collaborative competence in healthcare education. Sub-acute scenarios can supplement the more common approaches with acute care scenarios and aid in developing the collaborative competence required to work in healthcare teams.

Surgical helmets can be converted into efficient disinfectable powered air-purifying respirators.

BACKGROUND: Filtering facepiece respirators often fail to provide sufficient protection due to a poor fit. Powered air-purifying respirators (PAPRs) are not designed for healthcare personnel, and are challenging to disinfect. Surgical helmets (SH) are available in many United States hospitals but do not provide respiratory protection. Several modifications to SH have been suggested, but none are sufficiently compliant with safety and efficiency standards. The purpose of this investigation was the development of a filter adaptor, which converts SHs into efficient, safe, and disinfectable PAPRs. METHODS: Four critical features were investigated close to regulatory requirements: total inward leakage of particles, CO2 concentrations, intra-helmet differential pressure, and automated disinfection. RESULTS: The average total inward leakage in the 2 independent tests were 0.005% and 0.01%. CO2 concentrations were lower than in the original SH. The modification generates a positive differential pressure. The filter's performance was not compromised after 50 cycles in a sterilization machine. DISCUSSION: The modified SH provides several hundred times better protection than FFP-3 masks. CONCLUSIONS: Surgical helmets can be modified into safe, efficient, and disinfectable PAPRs, suitable for HCP and the operating room in particular. They can play a role in the preparedness for upcoming events requiring efficient respiratory protection.

Concomitant full-thickness cartilage lesions do not affect patient-reported outcomes at minimum 10-year follow-up after ACL reconstruction.

PURPOSE: To compare patients with a concomitant full-thickness cartilage lesion and anterior cruciate ligament (ACL) injury to patients with an isolated ACL injury at 10-15 years post ACL reconstruction. METHODS: This is a longitudinal follow-up of a cohort of 89 patients that were identified in the Norwegian National Knee Ligament Registry and included in the index study in 2007. The study group consisted of 30 patients that underwent ACL reconstruction and had a concomitant, isolated full-thickness cartilage lesion (International Cartilage Repair Society [ICRS] grade 3-4). Each study patient was matched with two control patients who underwent ACL reconstruction but had no cartilage lesions (ICRS grade 1-4) (n = 59). At a median follow-up of 10.2 years (range 9.9-15.6), 65 patients (74%) completed the Knee Injury and Osteoarthritis Outcome Score (KOOS), which was the main outcome measure, resulting in 23 pairs after matching. RESULTS: At a follow-up of 10-15 years after ACL reconstruction, no significant differences in KOOS were found between patients with a concomitant full-thickness cartilage lesion and patients without cartilage lesions. There was also no significant difference between the two groups when comparing the change over time in KOOS scores from preoperative to follow-up. Both groups showed significant improvement in all KOOS subscales from preoperative to follow-up, except for in the Symptoms subscale for the control group. The greatest improvement was in the QoL subscale for the study group. CONCLUSION: ACL-reconstructed patients with a full-thickness cartilage lesion did not report worse outcomes at 10-15 years after surgery compared with patients with an isolated ACL injury. Our findings support that there is no long-term negative effect of a concomitant cartilage lesion in an ACL-reconstructed knee. These findings should be considered when discussing treatment and informing about the expected long-term outcome after ACL reconstruction to patients with such combined injuries. LEVEL OF EVIDENCE: II.

Capillary function progressively deteriorates in prodromal Alzheimer's disease: A longitudinal MRI perfusion study.

Cardiovascular risk factors are associated with the development of Alzheimer's disease (AD), and increasing evidence suggests that cerebral microvascular dysfunction plays a vital role in the disease progression. Using magnetic resonance imaging, we investigated the two-year changes of the cerebral microvascular blood flow in 11 mild cognitively impaired (MCI) patients with prodromal AD compared to 12 MCI patients without evidence of AD and 10 cognitively intact age-matched controls. The pAD-MCI patients displayed widespread deterioration in microvascular cerebral perfusion associated with capillary dysfunction. No such changes were observed in the other two groups, suggesting that the dysfunction in capillary perfusion is linked to the AD pathophysiology. The observed capillary dysfunction may limit local oxygenation in AD leading to downstream ß-amyloid aggregation, tau hyperphosphorylation, neuroinflammation and neuronal dysfunction. The findings are in agreement with the capillary dysfunction hypothesis of AD, suggesting that increasing heterogeneity of capillary blood flow is a primary pathological event in AD.

Exploring healthcare students' interprofessional teamwork in primary care simulation scenarios: collaboration to create a shared treatment plan.

BACKGROUND: Primary care providers assume responsibility for patients with increasingly complex problems requiring interprofessional collaboration. Introducing interprofessional education in healthcare curricula prepares healthcare students for this reality. Solving simulation scenarios as an educational strategy is promoted to support interprofessional education in health care, and is mostly used in acute clinical situations. This paper aims to explore how healthcare students' actions influence interprofessional collaboration and treatment plan identification when they solve common, sub-acute patient scenarios in primary care situations. METHODS: Interaction analysis of video recordings from the simulation scenarios was performed with a focus on the students' joint actions; specifically how these actions unfold and how productive the students were in terms of developing treatment plans. RESULTS: We found variation in the groups' interactions, the paths they followed, and the quality of their knowledge output in their shared treatment plan. The groups with the capacity to collaborate and engage in sharing information, and explain and elaborate on concepts, were more successful in developing comprehensive treatment plans. Furthermore, these groups managed the duality of defining and solving the immediate problem and collaboratively preparing for future care. CONCLUSIONS: Analysis of the activities in our scenarios showed the students' potential to practice interprofessional collaboration. Our study illustrates that simulation of sub-acute scenarios in primary care is an underexplored but suitable arena to train communication and teamwork in complex situations. The simulation scenarios are also feasible for use on-site in an educational facility or in practice with minimal equipment and resources.

Time to maximum indocyanine green fluorescence of gastric sentinel lymph nodes and feasibility of combined indocyanine green/sodium fluorescein gastric lymphography.

PURPOSE: Indocyanine green (ICG) and sodium fluorescein (SF) are fluorescent dyes used for sentinel lymph node mapping. In oncological gastric surgery, ICG lymphography has increased the number of resected lymph nodes. However, the optimal time to administer ICG is unclear, and both preoperative and intraoperative injections have been practised. As dye spillage will diminish lymphogram visibility, a second dye with different excitation and emission spectra may present a clinical alternative. We measured the time until maximum ICG fluorescence of gastric sentinel lymph nodes and investigated the feasibility of combined lymphography with two fluorescent dyes: ICG and SF. METHODS: Ten Danish Landrace/Yorkshire pigs were used in this study. After completion of the laparoscopic setup, ICG and then SF were endoscopically injected into the gastric submucosa. Lymphograms for both dyes were recorded, and the time until maximum ICG sentinel lymph node fluorescence was determined. RESULTS: The mean time until maximum ICG fluorescence of gastric sentinel lymph nodes was 50 s (± 12.5), and the fluorescent signal then remained stable until the end of the recorded period (45 min). A lymphogram showing both ICG and SF was acquired for eight of the ten pigs. CONCLUSIONS: Because of the short time until maximum ICG fluorescence of sentinel lymph nodes, intraoperative injections could be a sufficient alternative to preoperative injections for oncological gastric surgery. Combined ICG and SF lymphography was feasible and resulted in clear lymphograms with no interference between the two dyes. The ability to use multiple dyes during a surgical procedure offers the exciting prospect of simultaneously assessing perfusion and performing fluorescence lymphography.

Mesenteric traction syndrome in pigs: A single-blinded, randomized controlled trial.

Background: Mesenteric traction syndrome is commonly observed in patients undergoing upper abdominal surgery and is associated with severe postoperative complications. A triad of hypotension, tachycardia, and facial flushing seems provoked by prostacyclin (PGI2) release from the gut in response to mesenteric traction. The administration of nonsteroidal anti-inflammatory drugs (NSAID) inhibits PGI2 release, stabilizing the hemodynamic response. Here, we examined the effect of mesenteric traction on splanchnic blood flow in pigs randomized to NSAID or placebo treatment. Materials and Methods: Twenty pigs were allocated to either ketorolac or placebo treatment. Five minutes of manual mesenteric traction was applied. Plasma 6-keto-PGF1α, a stable metabolite of PGI2, hemodynamic variables, and regional blood flow (laser speckle contrast imaging) to the liver, stomach, small intestine, upper lip, and snout (laser Doppler flowmetry) were recorded prior to traction and 5 and 30 minutes thereafter. Results: Both groups of pigs presented a decrease in systemic vascular resistance (P = .01), mean arterial blood pressure (P = .001), and blood flow in the gastric antrum (P = .002). Plasma 6-keto-PGF1α did not increase in either group (P = .195), and cardiac output, heart rate, central venous pressure, and blood flow to the liver, small intestine, upper lip, and snout remained unchanged. Conclusion: Mesenteric traction resulted in cardiovascular depression, including reduced blood flow in the gastric antrum. Plasma 6-keto-PGF1α did not increase, and ketorolac administration did not alter the response to mesenteric traction. Furthers studies are needed to identify which substance is responsible for eliciting the cardiovascular response to mesenteric traction in pigs.

KwARG: parsimonious reconstruction of ancestral recombination graphs with recurrent mutation.

MOTIVATION: The reconstruction of possible histories given a sample of genetic data in the presence of recombination and recurrent mutation is a challenging problem, but can provide key insights into the evolution of a population. We present KwARG, which implements a parsimony-based greedy heuristic algorithm for finding plausible genealogical histories (ancestral recombination graphs) that are minimal or near-minimal in the number of posited recombination and mutation events. RESULTS: Given an input dataset of aligned sequences, KwARG outputs a list of possible candidate solutions, each comprising a list of mutation and recombination events that could have generated the dataset; the relative proportion of recombinations and recurrent mutations in a solution can be controlled via specifying a set of 'cost' parameters. We demonstrate that the algorithm performs well when compared against existing methods. AVAILABILITY AND IMPLEMENTATION: The software is available at https://github.com/a-ignatieva/kwarg. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hypotension Associated with MTS is Aggravated by Early Activation of TEA During Open Esophagectomy.

OBJECTIVE: A mesenteric traction syndrome (MTS) is elicited by prostacyclin (PGI2)-induced vasodilation and identified by facial flushing, tachycardia, and hypotension during abdominal surgery. We evaluated whether thoracic epidural anesthesia (TEA) influences the incidence of MTS. DESIGN: Randomized, blinded controlled trial. SETTING: Single-center university hospital. PARTICIPANTS: Fifty patients undergoing open esophagectomy. INTERVENTIONS: Patients were randomized to either early (EA, after induction of general anesthesia) or late activation of TEA (LA, after re-established gastric continuity). Plasma 6-keto-PGF1α, a stable metabolite of PGI2 and interleukine-6 (IL6) were measured in plasma during surgery along with hemodynamic variables and MTS graded according to facial flushing together with plasma C-reactive protein on the third post-operative day. RESULTS: Forty-five patients met the inclusion criteria. Development of MTS tended to be more prevalent with EA (n=13/25 [52%]) than with LA TEA (n=5/20 [25%], p=0.08). For patients who developed MTS, there was a transient increase in plasma 6-keto-PGF1α by 15 min of surgery and plasma IL6 (p<0.001) as C-reactive protein (P<0.009) increased. EA TEA influenced the amount of phenylephrine needed to maintain mean arterial pressure >60 mmHg in patients who developed MTS (0.16 [0.016-0.019] mg/min vs MTS and LA TEA 0.000 [0.000-0.005] mg/min, p<0.001). CONCLUSION: The incidence of MTS is not prevented by TEA in patients undergoing open esophagectomy. On the contrary, the risk of hypotension is increased in patients exposed to TEA during surgery, and the results suggest that it is advantageous to delay activation of TEA. Also, MTS seems to be associated with a systemic inflammatory response, maybe explaining the aggravated post-operative outcome.

Selective release of gastrointestinal hormones induced by an orally active GPR39 agonist.

OBJECTIVES: Obesity is a complex disease associated with a high risk of comorbidities. Gastric bypass surgery, an invasive procedure with low patient eligibility, is currently the most effective intervention that achieves sustained weight loss. This beneficial effect is attributed to alterations in gut hormone signaling. An attractive alternative is to pharmacologically mimic the effects of bariatric surgery by targeting several gut hormonal axes. The G protein-coupled receptor 39 (GPR39) expressed in the gastrointestinal tract has been shown to mediate ghrelin signaling and control appetite, food intake, and energy homeostasis, but the broader effect on gut hormones is largely unknown. A potent and efficacious GPR39 agonist (Cpd1324) was recently discovered, but the in vivo function was not addressed. Herein we studied the efficacy of the GPR39 agonist, Cpd1324, on metabolism and gut hormone secretion. METHODS: Body weight, food intake, and energy expenditure in GPR39 agonist-treated mice and GPR39 KO mice were studied in calorimetric cages. Plasma ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) levels were measured. Organoids generated from murine and human small intestine and mouse colon were used to study GLP-1 and PYY release. Upon GPR39 agonist administration, dynamic changes in intracellular GLP-1 content were studied via immunostaining and changes in ion transport across colonic mucosa were monitored in Ussing chambers. The G protein activation underlying GPR39-mediated selective release of gut hormones was studied using bioluminescence resonance energy transfer biosensors. RESULTS: The GPR39 KO mice displayed a significantly increased food intake without corresponding increases in respiratory exchange ratios or energy expenditure. Oral administration of a GPR39 agonist induced an acute decrease in food intake and subsequent weight loss in high-fat diet (HFD)-fed mice without affecting their energy expenditure. The tool compound, Cpd1324, increased GLP-1 secretion in the mice as well as in mouse and human intestinal organoids, but not in GPR39 KO mouse organoids. In contrast, the GPR39 agonist had no effect on PYY or GIP secretion. Transepithelial ion transport was acutely affected by GPR39 agonism in a GLP-1- and calcitonin gene-related peptide (CGRP)-dependent manner. Analysis of Cpd1324 signaling properties showed activation of Gαq and Gαi/o signaling pathways in L cells, but not Gαs signaling. CONCLUSIONS: The GPR39 agonist described in this study can potentially be used by oral administration as a weight-lowering agent due to its stimulatory effect on GLP-1 secretion, which is most likely mediated through a unique activation of Gα subunits. Thus, GPR39 agonism may represent a novel approach to effectively treat obesity through selective modulation of gastrointestinal hormonal axes.

Fixation of Acute Chondral Fractures in Adolescent Knees.

OBJECTIVES: Chondral fractures are focal cartilage lesions without osseous attachment, most commonly seen in adolescent knees. They have limited capacity for intrinsic healing and traditional treatment has been removal of loose fragments. However, case reports of successful healing after fixation indicate that repair of the joint surface is possible. We wanted to evaluate the outcome in a cohort of patients who underwent fixation of acute chondral fractures in the knee. DESIGN: Patients treated with fixation of a chondral fracture in the knee at our institution were invited to participate in a follow-up study. The mechanism of injury, fragment properties and complications were registered. Patients completed KOOS (Knee Injury and Osteoarthritis Outcome Score) and Lysholm questionnaires and performed a validated single leg hop test. Magnetic resonance imaging (MRI) was used to assess healing of the defect and the quality of the cartilage. RESULTS: Ten patients with a median age at surgery of 15 years (12-17 years) and median follow-up of 5 years (2-9 years) were assessed. The lesions were located on the patella (n = 7), the trochlea (n = 2), and the lateral femoral condyle (n = 1). Median lesion size was 250 mm2 (1.9-6.0 cm2) All patients were treated within 2 months of injury (4-58 days). All patients returned to preinjury level of sports and MRI showed retained fragments that integrated well with surrounding cartilage at follow-up. Mean Lysholm score at follow-up was 90 (73-100). CONCLUSION: Fixation of traumatic chondral-only fragments using bioabsorbable implants may result in successful healing in adolescent patients and should be considered a treatment option in acute injuries.

Impaired perfusion and capillary dysfunction in prodromal Alzheimer's disease.

INTRODUCTION: Cardiovascular disease increases the risk of developing Alzheimer's disease (AD), and growing evidence suggests an involvement of cerebrovascular pathology in AD. Capillary dysfunction, a condition in which capillary flow disturbances rather than arterial blood supply limit brain oxygen extraction, could represent an overlooked vascular contributor to neurodegeneration. We examined whether cortical capillary transit-time heterogeneity (CTH), an index of capillary dysfunction, is elevated in amyloid-positive patients with mild cognitive impairment (prodromal AD [pAD]). METHODS: We performed structural and perfusion weighted MRI in 22 pAD patients and 21 healthy controls. RESULTS: We found hypoperfusion, reduced blood volume, and elevated CTH in the parietal and frontal cortices of pAD-patients compared to controls, while only the precuneus showed focal cortical atrophy. DISCUSSION: We propose that microvascular flow disturbances antedate cortical atrophy and may limit local tissue oxygenation in pAD. We speculate that capillary dysfunction contributes to the development of neurodegeneration in AD.

The Incidence of Free Peritoneal Tumor Cells before and after Neoadjuvant Chemotherapy in Gastroesophageal Junction Cancer.

CONTEXT: The utility of peritoneal washing cytology in patients with gastroesophageal junction cancer has not been thoroughly evaluated. AIMS: The study aimed to determine the incidence of free peritoneal tumor cells by peritoneal washing cytology before and after neoadjuvant chemotherapy using conventional cytopathological methods and immunohistochemical staining for the analysis of peritoneal washings. SETTINGS AND DESIGN: A prospective study conducted at a single tertiary referral hospital. MATERIALS AND METHODS: Patients with gastroesophageal junction cancer and without suspicion of intra- or extraabdominal metastases before the staging laparoscopy were prospectively and consecutively enrolled. Peritoneal washing cytology was performed at staging laparoscopy (primary cytology) and after neoadjuvant chemotherapy during robot-assisted or open resection (secondary cytology). Peritoneal fluid samples were analyzed by conventional cytology and an immunohistochemical panel. RESULTS: Overall, 81 patients met the primary inclusion criteria. During primary cytology, positive cytology without overt metastases (C1M0) was detected in three patients (3.8%) while five patients (6.3%) had overt intra-abdominal metastases but negative cytology (C0M1). None of the patients with C1M0 underwent surgery due to extra-abdominal (n = 1) or intra-abdominal metastases (n = 2), and the overall survival was 4, 7, and 14 months. During secondary cytology, no patients with free peritoneal tumor cells were identified, but seven patients were classified as C0M1 (10.9%). CONCLUSIONS: The incidence of C1M0 was 3.8% and 0% before and after neoadjuvant chemotherapy, respectively in patients with gastroesophageal junction cancer. Free peritoneal tumor cells were not identified in several patients with intra-abdominal metastases suggesting that peritoneal washing cytology with conventional cytology and immunohistochemical staining lack sensitivity.

Development of a severe mesenteric traction syndrome during major abdominal surgery is associated with increased postoperative morbidity: Secondary data analysis on prospective cohorts.

PURPOSE: MTS is elicited during open abdominal surgery and is characterized by facial flushing, hypotension, and tachycardia in response to the release of prostacyclin (PGI2) to plasma. MTS seems to affect postoperative morbidity, but data from larger cohorts are lacking. We aimed to determine the impact of severe mesenteric traction syndrome (MTS) on postoperative morbidity in patients undergoing open upper gastrointestinal surgery. METHODS: The study was a secondary analysis of data from three cohorts (n = 137). The patients were graded for severity of MTS intraoperatively, and hemodynamic variables and blood samples for plasma 6-keto-PGF1α, a stable metabolite of PGI2, were obtained at defined time points. Postoperative morbidity was evaluated by the comprehensive complication index (CCI) and the Dindo-Clavien classification (DC). RESULTS: Patients undergoing either esophagectomy (n = 70), gastrectomy (n = 22), liver- (n = 23), or pancreatic resection (n = 22) were included. Severe MTS was significantly associated with increased postoperative morbidity, i.e., CCI ≥ 26.2 (OR 3.06 [95% CI 1.1-6.6]; p = 0.03) and risk of severe complications, i.e., DC ≥3b (OR 3.1 [95% CI 1.2-8.2]; p = 0.023). Furthermore, patients with severe MTS had increased length of stay (OR 10.1 [95% CI 1.9-54.3]; p = 0.007) and were more likely to be admitted to the intensive care unit (OR = 7.3 [95% CI 1.3-41.9]; p = 0.027), but there was no difference in 1-year mortality. CONCLUSION: Occurrence of severe MTS during upper gastrointestinal surgery is associated with increased postoperative morbidity as indicated by an increased rate of severe complications, length of stay, and admission to the ICU. It remains to be determined whether inhibition of MTS enhances postoperative recovery.

Effect of hypotensive hypovolemia and thoracic epidural anesthesia on plasma pro-atrial natriuretic peptide to indicate deviations in central blood volume in pigs: a blinded, randomized controlled trial.

PURPOSE: Changes in plasma pro-atrial natriuretic peptide (proANP) may indicate deviations in the central blood volume (CBV). We evaluated the plasma proANP response to hypotensive hypovolemia under the influence of thoracic epidural anesthesia (TEA) in pigs. We hypothesized that plasma proANP would decrease in response to hypotensive hypovolemia and that TEA would aggravate the proANP response, reflecting a further decrease in CBV. DESIGN: Randomized, blinded, controlled trial. SETTING: A university-affiliated experimental facility. PARTICIPANTS: Twenty pigs randomized to administration of saline (placebo) or bupivacaine with morphine (TEA) in the epidural space at Th8-Th10. INTERVENTIONS: Relative hypovolemia was established by an inflatable Foley catheter positioned in the inferior caval vein just below the heart (caval obstruction), and hemorrhage-induced hypovolemia was by withdrawal of blood from the femoral artery, both aiming at a mean arterial pressure (MAP) of 50-60 mmHg. Hemodynamic variables and plasma proANP were determined before and after the interventions. RESULTS: Caval obstruction and withdrawal of blood reduced MAP to 50-60 mmHg. Accordingly, cardiac output, central venous pressure, and mixed venous oxygen saturation decreased (p<0.05). Yet, plasma proANP was stable after both caval obstruction (TEA: 72 [63-78] to 80 pmol/L [72-85], p=0.09 and placebo: 64 [58-76] to 69 pmol/L [57-81], p=0.06) and withdrawal of blood (TEA: 74 [73-83] to 79 pmol/L [77-87], p=0.07 and placebo: 64 [56-77] to 67 pmol/L [58-78], p=0.15). CONCLUSION: Plasma proANP was stable in response to relative and hemorrhage-induced hypovolemia to a MAP of 50-60 mmHg, and the response was independent of TEA. The findings suggest that alterations in plasma proANP do not follow deviations in CBV during hypotensive hypovolemia in pigs.

Effect of early versus delayed activation of thoracic epidural anesthesia on plasma pro-atrial natriuretic peptide to indicate deviations in central blood volume during esophagectomy.

BACKGROUND AND OBJECTIVES: A side effect to thoracic epidural anesthesia (TEA) is hypotension induced by central hypovolemia. This study addressed whether early activation (EA) versus late activation (LA) of TEA affects plasma pro-atrial natriuretic peptide (proANP) reflecting deviations in the central blood volume (CBV). We hypothesized that EA TEA would reduce plasma proANP, thus reflecting a decrease in CBV. METHODS: A randomized, controlled, single-blinded trial was conducted. Patients undergoing open esophagectomy were randomized to EA (n=25, after induction of general anesthesia) or LA TEA (n=25, after re-established gastric continuity) with the epidural catheter placed at the interspaces Th7-8 or Th8-9. Plasma proANP was determined repetitively along with hemodynamic variables and administration of fluid/vasopressors as postoperative complications were noted. RESULTS: With EA TEA, plasma proANP decreased following induction of anesthesia to the end of surgery (13%; 113±68 to 99±49 pmol/L; p=0.026), but that was not the case in the LA group (3%; 97±44 to 94±49 pmol/L; p=0.565) despite equal fluid balance (+1584±582 vs +1560±563 mL; p=0.888). Accordingly, the EA group required excessive treatment with vasopressors to maintain MAP >60 mm Hg during surgery (2.7±2 vs 1.6±1.4 ephedrine boluses; p=0.033 and infusion of phenylephrine for 216±86 vs 58±91 min; p<0.001). Plasma proANP and fluid balance were correlated only for EA patients (r=0.44; 95% CI 0.04 to 0.91; p=0.033). CONCLUSIONS: EA TEA reduces plasma proANP indicating that CBV becomes affected. Based on a correlation between plasma proANP and fluid balance, a 2000 mL volume surplus of lactated Ringer's solution is required to maintain plasma proANP stable during open esophagectomy. TRIAL REGISTRATION NUMBER: 2014-002036-14 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-002036-14).