The role of ureteric indocyanine green fluorescence in colorectal surgery: a retrospective cohort study.

BACKGROUND: Ureteric injury (UI) is an infrequent but serious complication of colorectal surgery. Prophylactic ureteric stenting is employed to avoid UI, yet its efficacy remains debated. Intraoperative indocyanine green fluorescence imaging (ICG-FI) has been used to facilitate ureter detection. This study aimed to investigate the role of ICG-FI in identification of ureters during colorectal surgery and its impact on the incidence of UI. METHODS: A retrospective cohort study involving 556 consecutive patients who underwent colorectal surgery between 2018 and 2023 assessed the utility of routine prophylactic ureteric stenting with adjunctive ICG-FI. Patients with ICG-FI were compared to those without ICG-FI. Demographic data, operative details, and postoperative morbidity were analyzed. Statistical analysis included univariable regression. RESULTS: Ureteric ICG-FI was used in 312 (56.1%) patients, whereas 43.9% were controls. Both groups were comparable in terms of demographics except for a higher prevalence of prior abdominal surgeries in the ICG-FI group. Although intraoperative visualization was significantly higher in the ICG-FI group (95.3% vs 89.1%; p = 0.011), the incidence of UI was similar between groups (0.3% vs 0.8%; p = 0.585). Postoperative complications were similar between the two groups. Median stent insertion time was longer in the ICG-FI group (32 vs 25 min; p = 0.001). CONCLUSION: Ureteric ICG-FI improved intraoperative visualization of the ureters but was not associated with a reduced UI rate. Median stent insertion time increased with use of ureteric ICG-FI, but total operative time did not. Despite its limitations, this study is the largest of its kind suggesting that ureteric ICG-FI may be a valuable adjunct to facilitate  ureteric visualization during colorectal surgery.

When is neoadjuvant chemotherapy indicated in rectal neuroendocrine tumors? An analysis of the National Cancer Database.

BACKGROUND: Rectal neuroendocrine tumors (rNET) are rare and challenging to manage. While most patients with small rNET can be definitively treated with local excision, the role of chemotherapy in general and neoadjuvant therapy particularly in managing advanced rNET has not been well established. Therefore, this study aimed to determine which patients with rNET may gain a survival benefit from neoadjuvant chemotherapy. METHODS: A retrospective cohort analysis of all patients who underwent surgical resection of rNET in the US National Cancer Database (NCDB) (2004-2019) was performed. First, univariate and multivariate Cox regression analyses were performed to determine the independent predictors of poor overall survival (OS) and define the high-risk groups. Afterward, stratified OS analyses were performed for each high-risk group to assess whether neoadjuvant chemotherapy had a survival benefit in each group. RESULTS: A total of 1837 patients (49.8% female; mean age 56.6 ± 12.3 years) underwent radical resection of a rNET. Tumors > 20 mm in size, clinical T4 tumors, poorly differentiated tumors, and metastatic disease were independent predictors of worse OS and were defined as high-risk groups. Neoadjuvant chemotherapy did not have a significant survival benefit in any of the high-risk groups, except for patients with high-grade rNETs where neoadjuvant therapy significantly improved OS to a mean of 30.9 months compared with 15.9 months when neoadjuvant therapy was not given (p = 0.006). CONCLUSIONS: Neoadjuvant chemotherapy improved the OS of patients with high-grade rNET by 15 months and may be indicated for this group.

Combined use of long-lasting insecticidal nets and Bacillus thuringiensis israelensis larviciding, a promising integrated approach against malaria transmission in northern Côte d'Ivoire.

BACKGROUND: The recent reduction in malaria burden in Côte d'Ivoire is largely attributable to the use of long-lasting insecticidal nets (LLINs). However, this progress is threatened by insecticide resistance and behavioral changes in Anopheles gambiae sensu lato (s.l.) populations and residual malaria transmission, and complementary tools are required. Thus, this study aimed to assess the efficacy of the combined use of LLINs and Bacillus thuringiensis israelensis (Bti), in comparison with LLINs. METHODS: This study was conducted in the health district of Korhogo, northern Côte d'Ivoire, within two study arms (LLIN + Bti arm and LLIN-only arm) from March 2019 to February 2020. In the LLIN + Bti arm, Anopheles larval habitats were treated every fortnight with Bti in addition to the use of LLINs. Mosquito larvae and adults were sampled and identified morphologically to genus and species using standard methods. The members of the An. gambiae complex were determined using a polymerase chain reaction technique. Plasmodium infection in An. gambiae s.l. and malaria incidence in local people was also assessed. RESULTS: Overall, Anopheles spp. larval density was lower in the LLIN + Bti arm 0.61 [95% CI 0.41-0.81] larva/dip (l/dip) compared with the LLIN-only arm 3.97 [95% CI 3.56-4.38] l/dip (RR = 6.50; 95% CI 5.81-7.29; P < 0.001). The overall biting rate of An. gambiae s.l. was 0.59 [95% CI 0.43-0.75] biting/person/night in the LLIN + Bti arm against 2.97 [95% CI 2.02-3.93] biting/person/night in LLIN-only arm (P < 0.001). Anopheles gambiae s.l. was predominantly identified as An. gambiae sensu stricto (s.s.) (95.1%, n = 293), followed by Anopheles coluzzii (4.9%; n = 15). The human-blood index was 80.5% (n = 389) in study area. EIR was 1.36 infected bites/person/year (ib/p/y) in the LLIN + Bti arm against 47.71 ib/p/y in the LLIN-only arm. Malaria incidence dramatically declined from 291.8‰ (n = 765) to 111.4‰ (n = 292) in LLIN + Bti arm (P < 0.001). CONCLUSIONS: The combined use of LLINs with Bti significantly reduced the incidence of malaria. The LLINs and Bti duo could be a promising integrated approach for effective vector control of An. gambiae for elimination of malaria.

The correlation between carotid artery Doppler and stroke volume during central blood volume loss and resuscitation.

BACKGROUND: Using peripheral arteries to infer central hemodynamics is common among hemodynamic monitors. Doppler ultrasound of the common carotid artery has been used in this manner with conflicting results. We investigated the relationship between changing common carotid artery Doppler measures and stroke volume (SV), hypothesizing that more consecutively-averaged cardiac cycles would improve SV-carotid Doppler correlation. METHODS: Twenty-seven healthy volunteers were recruited and studied in a physiology laboratory. Carotid artery Doppler pulse was measured with a wearable, wireless ultrasound during central hypovolemia and resuscitation induced by a stepped lower body negative pressure protocol. The change in maximum velocity time integral (VTI) and corrected flow time of the carotid artery (ccFT) were compared with changing SV using repeated measures correlation. RESULTS: In total, 73,431 cardiac cycles were compared across 27 subjects. There was a strong linear correlation between changing SV and carotid Doppler measures during simulated hemorrhage (repeated-measures linear correlation [Rrm ]=0.91 for VTI; 0.88 for ccFT). This relationship improved with larger numbers of consecutively-averaged cardiac cycles. For ccFT, beyond four consecutively-averaged cardiac cycles the correlation coefficient remained strong (i.e., Rrm of at least 0.80). For VTI, the correlation coefficient with SV was strong for any number of averaged cardiac cycles. For both ccFT and VTI, Rrm remained stable around 25 consecutively-averaged cardiac cycles. CONCLUSIONS: There was a strong linear correlation between changing SV and carotid Doppler measures during central blood volume loss. The strength of this relationship was dependent upon the number of consecutively-averaged cardiac cycles.

The left ventricular outflow tract and carotid artery velocity time integrals.

The left ventricular outflow tract velocity time integral (LVOT VTI) is commonly used in the intensive care unit as a measure of stroke volume (SV) and how the SV changes in response to an intervention; therefore, the LVOT VTI is used to guide intravenous fluid management. Various peripheral Doppler surrogates are proposed to infer the LVOT VTI (e.g., measures from the common carotid artery). A recently-described, novel method of insonation has an excellent ability to detect change in the LVOT VTI. This approach raises important facets of Doppler flow and insonation error, as well as the general principles at play when using a peripheral artery to infer changes from the left ventricle. Relating the VTI of a peripheral artery to the LVOT VTI was recently described mathematically and may help clinicians think about the Doppler relationship between central and peripheral flow.

Simultaneous Venous-Arterial Doppler Ultrasound During Early Fluid Resuscitation to Characterize a Novel Doppler Starling Curve: A Prospective Observational Pilot Study.

Background: The likelihood of a patient being preload responsive-a state where the cardiac output or stroke volume (SV) increases significantly in response to preload-depends on both cardiac filling and function. This relationship is described by the canonical Frank-Starling curve. Research Question: We hypothesize that a novel method for phenotyping hypoperfused patients (ie, the "Doppler Starling curve") using synchronously measured jugular venous Doppler as a marker of central venous pressure (CVP) and corrected flow time of the carotid artery (ccFT) as a surrogate for SV will refine the pretest probability of preload responsiveness/unresponsiveness. Study Design and Methods: We retrospectively analyzed a prospectively collected convenience sample of hypoperfused adult emergency department (ED) patients. Doppler measurements were obtained before and during a preload challenge using a wireless, wearable Doppler ultrasound system. Based on internal jugular and carotid artery Doppler surrogates of CVP and SV, respectively, we placed hemodynamic assessments into quadrants (Qx) prior to preload augmentation: low CVP with normal SV (Q1), high CVP and normal SV (Q2), low CVP and low SV (Q3) and high CVP and low SV (Q4). The proportion of preload responsive and unresponsive assessments in each quadrant was calculated based on the maximal change in ccFT (ccFTΔ) during either a passive leg raise or rapid fluid challenge. Results: We analyzed 41 patients (68 hemodynamic assessments) between February and April 2021. The prevalence of each phenotype was: 15 (22%) in Q1, 8 (12%) in Q2, 39 (57%) in Q3, and 6 (9%) in Q4. Preload unresponsiveness rates were: Q1, 20%; Q2, 50%; Q3, 33%, and Q4, 67%. Interpretation: Even fluid naïve ED patients with sonographic estimates of low CVP have high rates of fluid unresponsiveness, making dynamic testing valuable to prevent ineffective IVF administration.

Gracilis muscle interposition for pouch-vaginal fistulas: a single-centre cohort study and literature review.

BACKGROUND: First described by Parks and Nicholls in 1978, the ileal pouch-anal anastomosis (IPAA) has revolutionized the treatment of mucosal ulcerative colitis (MUC) and familial adenomatous polyposis (FAP). IPAA is fraught with complications, one of which is pouch-vaginal fistulas (PVF), a rare but challenging complication noted in 3.9-15% of female patients. Surgical treatment success approximates 50%. Gracilis muscle interposition (GMI) is a promising technique that has shown good results with other types of perineal fistulas. We present the results from our institution and a comprehensive literature review. METHODS: A retrospective observational study including all patients with a PVF treated with GMI at our institution from December 2018-January 2000. Primary outcome was complete healing after ileostomy closure. RESULTS: Nine patients were included. Eight of nine IPAAs (88.9%) were performed for MUC, and one for FAP. A subsequent diagnosis of Crohn's disease was made in five patients. Initial success occurred in two patients (22.2%), one patient was lost to follow-up and seven patients, after further procedures, ultimately achieved healing (77.8%). Four of five patients with Crohn's achieved complete healing (80%). CONCLUSION: Surgical healing rates quoted in the literature for PVFs are approximately 50%. The initial healing rate was 22.2% and increased to 77.8% after subsequent surgeries, while it was 80% in patients with Crohn's disease. Given this, gracilis muscle interposition may have a role in the treatment of pouch-vaginal fistulas.

Unifying Fluid Responsiveness and Tolerance With Physiology: A Dynamic Interpretation of the Diamond-Forrester Classification.

Point of care ultrasound (POCUS) is a first-line tool to assess hemodynamically unstable patients, however, there is confusion surrounding intertwined concepts such as: "flow," "congestion," "fluid responsiveness (FR)," and "fluid tolerance." We argue that the Frank-Starling relationship is clarifying because it describes the interplay between "congestion" and "flow" on the x-axis and y-axis, respectively. Nevertheless, a single, simultaneous assessment of congestion and flow via POCUS remains a static approach. To expand this, we propose a two-step process. The first step is to place the patient on an ultrasonographic Diamond-Forrester plot. The second step is a dynamic assessment for FR (e.g., passive leg raise), which individualizes therapy across the arc of critical illness.

Inferior Vena Caval Measures Do Not Correlate with Carotid Artery Corrected Flow Time Change Measured Using a Wireless Doppler Patch in Healthy Volunteers.

(1) Background: The inspiratory collapse of the inferior vena cava (IVC), a non-invasive surrogate for right atrial pressure, is often used to predict whether a patient will augment stroke volume (SV) in response to a preload challenge. There is a correlation between changing stroke volume (SV∆) and corrected flow time of the common carotid artery (ccFT∆). (2) Objective: We studied the relationship between IVC collapsibility and ccFT∆ in healthy volunteers during preload challenges. (3) Methods: A prospective, observational, pilot study in euvolemic, healthy volunteers with no cardiovascular history was undertaken in a local physiology lab. Using a tilt-table, we studied two degrees of preload augmentation from (a) supine to 30-degrees head-down and (b) fully-upright to 30-degrees head down. In the supine position, % of IVC collapse with respiration, sphericity index and portal vein pulsatility was calculated. The common carotid artery Doppler pulse was continuously captured using a wireless, wearable ultrasound system. (4) Results: Fourteen subjects were included. IVC % collapse with respiration ranged between 10% and 84% across all subjects. Preload responsiveness was defined as an increase in ccFT∆ of at least 7 milliseconds. A total of 79% (supine baseline) and 100% (head-up baseline) of subjects were preload-responsive. No supine venous measures (including IVC % collapse) were significantly related to ccFT∆. (5) Conclusions: From head-up baseline, 100% of healthy subjects were 'preload-responsive' as per the ccFT∆. Based on the 42% and 25% IVC collapse thresholds in the supine position, only 50% and 71% would have been labeled 'preload-responsive'.

A framework for heart-lung interaction and its application to prone position in the acute respiratory distress syndrome.

While both cardiac output (Qcirculatory) and right atrial pressure (PRA) are important measures in the intensive care unit (ICU), they are outputs of the system and not determinants. That is to say, in a model of the circulation wherein venous return and cardiac function find equilibrium at an 'operating point' (OP, defined by the PRA on the x-axis and Qcirculatory on the y-axis) both the PRA and Qcirculatory are, necessarily, dependent variables. A simplified geometrical approximation of Guyton's model is put forth to illustrate that the independent variables of the system are: 1) the mean systemic filling pressure (PMSF), 2) the pressure within the pericardium (PPC), 3) cardiac function and 4) the resistance to venous return. Classifying independent and dependent variables is clinically-important for therapeutic control of the circulation. Recent investigations in patients with acute respiratory distress syndrome (ARDS) have illuminated how PMSF, cardiac function and the resistance to venous return change when placing a patient in prone. Moreover, the location of the OP at baseline and the intimate physiological link between the heart and the lungs also mediate how the PRA and Qcirculatory respond to prone position. Whereas turning a patient from supine to prone is the focus of this discussion, the principles described within the framework apply equally-well to other more common ICU interventions including, but not limited to, ventilator management, initiating vasoactive medications and providing intravenous fluids.

Leaf acclimation to soil flooding and light availability underlies photosynthetic capacity of Lindera melissifolia, an endangered shrub of bottomland forests in the Mississippi Alluvial Valley, USA.

Lindera melissifolia is an endangered shrub indigenous to the broadleaf forest of the Mississippi Alluvial Valley (MAV). In this region, extant colonies of the species are found in periodically ponded habitats where a diversity of broadleaf trees can form well-developed overstory and sub-canopies-these habitat characteristics suggest that soil flooding and light availability are primary drivers of L. melissifolia ecophysiology. To understand how these two factors affect its photosynthetic capacity, we quantified leaf characteristics and photosynthetic response of plants grown in a large-scaled, field setting of three distinct soil flooding levels (no flood, 0 day; short-term flood, 45 days; and extended flood, 90 days) each containing three distinct light availability levels (high light, 30% shade cloth; intermediate light, 63% shade cloth; and low light, 95% shade cloth). Lindera melissifolia leaves showed marked plasticity to interacting effects of flooding and light with lamina mass per unit area (Lm/a) varying 78% and total nitrogen content per unit area (Na) varying 63% from the maximum. Photosynthetic capacity (A1800-a) ranged 123% increasing linearly with Na from low to high light. Extended flooding decreased the slope of this relationship 99% through a reduction in N availability and metabolic depression of A1800-a relative to Na. However, neither soil flooding nor light imposed an additive limitation on photosynthetic capacity when the other factor was at its most stressful level, and the A1800-a-Na relationship for plants that experienced short-term flooding suggested post-flood acclimation in photosynthetic capacity was approaching the maximal level under respective light environments. Our findings provide evidence for wide plasticity and acclimation potential of L. melissifolia photosynthetic capacity, which supports active habitat management, such as manipulation of stand structure for improved understory light environments, to benefit long-term conservation of the species in the MAV.

Simultaneous venous-arterial Doppler during preload augmentation: illustrating the Doppler Starling curve.

Providing intravenous (IV) fluids to a patient with signs or symptoms of hypoperfusion is common. However, evaluating the IV fluid 'dose-response' curve of the heart is elusive. Two patients were studied in the emergency department with a wireless, wearable Doppler ultrasound system. Change in the common carotid arterial and internal jugular Doppler spectrograms were simultaneously obtained as surrogates of left ventricular stroke volume (SV) and central venous pressure (CVP), respectively. Both patients initially had low CVP jugular venous Doppler spectrograms. With preload augmentation, only one patient had arterial Doppler measures indicative of significant SV augmentation (i.e., 'fluid responsive'). The other patient manifested diminishing arterial response, suggesting depressed SV (i.e., 'fluid unresponsive') with evidence of ventricular asynchrony. In this short communication, we describe how a wireless, wearable Doppler ultrasound simultaneously tracks surrogates of cardiac preload and output within a 'Doppler Starling curve' framework; implications for IV fluid dosing are discussed.

Carotid Artery Corrected Flow Time Measured by Wearable Doppler Ultrasound Accurately Detects Changing Stroke Volume During the Passive Leg Raise in Ambulatory Volunteers.

BACKGROUND: The change in the corrected flow time of the common carotid artery (ccFTΔ) has been used as a surrogate of changing stroke volume (SVΔ) in the critically-ill. Thus, this relatively easy-to-obtain Doppler measure may help clinicians better define the intended effect of intravenous fluids. Yet the temporal evolution of SVΔ and ccFTΔ has not been reported in volunteers undergoing a passive leg raise (PLR). METHODS: We recruited clinically-euvolemic, non-fasted, adult, volunteers in a local physiology lab to perform 2 PLR maneuvers, each separated by a 5 minute 'wash-out'. During each PLR, SV was measured by a non-invasive pulse contour analysis device. SV was temporally-synchronized with a wireless, wearable Doppler ultrasound worn over the common carotid artery that continuously measured ccFT. RESULTS: 36 PLR maneuvers were obtained across 19 ambulatory volunteers. 8856 carotid Doppler cardiac cycles were analyzed. The ccFT increased nearly ubiquitously during the PLR and within 40-60 seconds of PLR onset; the rise in SV from the pulse contour device was more gradual. SVΔ by +5% and +10% were both detected by a +7% ccFTΔ with sensitivities, specificities and areas under the receiver operator curve of 59%, 95% and 0.77 (p < 0.001) and 66%, 76% and 0.73 (p < 0.001), respectively. CONCLUSIONS: The ccFTΔ during the PLR in ambulatory volunteers was rapid and sustained. Within the limits of precision for detecting a clinically-significant rise in SV by a non-invasive pulse contour analysis device, simultaneously-acquired ccFT from a wireless, wearable ultrasound system was accurate at detecting 'preload responsiveness'.