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Abstract Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery.

Abstract Liver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution. Thus, drug delivery varies widely, highly-dependent upon technique. An X-ray imageable poloxamer 407 (POL)-based drug delivery gel was developed and characterized, enabling real-time feedback. Utilizing three needle devices, POL or a control iodinated contrast solution were injected into an ex vivo bovine liver. The 3D distribution was assessed with cone beam computed tomography (CBCT). The 3D distribution of POL gels demonstrated localized spherical morphologies regardless of the injection rate. In addition, the gel 3D conformal distribution could be intentionally altered, depending on the injection technique. When doxorubicin (DOX) was loaded into the POL and injected, DOX distribution on optical imaging matched iodine distribution on CBCT suggesting spatial alignment of DOX and iodine localization in tissue. The controllability and localized deposition of this formulation may ultimately reduce the dependence on operator technique, reduce systemic side effects, and facilitate reproducibility across treatments, through more predictable standardized delivery.

The stiffness of the extracellular matrix plays a crucial role in cell motility and spreading, influencing cell morphology through cytoskeleton organization and transmembrane proteins’ expression. In this context, mechanical characterization of both cells and the extracellular matrix gains prominence for enhanced diagnostics and clinical decision-making. Here, we investigate the combined effect of mechanotransduction and ionizing radiations on altering cells’ mechanical properties, analysing mammary cell lines (MCF10A and MDA-MB-231) after X-ray radiotherapy (2 and 10 Gy). We found that ionizing radiations sensitively affect adenocarcinoma cells cultured on substrates mimicking cancerous tissue stiffness (15 kPa), inducing an increased structuration of paxillin-rich focal adhesions and cytoskeleton: this process translates in the augmentation of tension at the actin filaments level, causing cellular stiffness and consequently affecting cytoplasmatic/nuclear morphologies. Deeper exploration of the intricate interplay between mechanical factors and radiation should provide novel strategies to orient clinical outcomes.

Abstract The biological effects of ionizing radiation are exploited in the clinical practice of radiotherapy to destroy tumour cells while sparing the surrounding normal tissue. While most of the radiotherapy research focused on DNA damage and repair, recently a great attention is going to cells' interactions with the mechanical microenvironment of both malignant and healthy tissues after exposure. In fact, the stiffness of the extracellular matrix can modify cells' motility and spreading through the modulation of transmembrane proteins and surface receptors' expression, such as CD-44. CD-44 receptor has held much interest also in targeted-therapy due to its affinity with hyaluronic acid, which can be used to functionalize biodegradable nanoparticles loaded with chemotherapy drugs for targeted therapy. We evaluated changes in CD-44 expression in two mammary carcinoma cell lines (MCF10A and MDA-MB-231) after exposure to X-ray (2 or 10 Gy). To explore the role of the mechanical microenvironment, we mimicked tissues' stiffness with polyacrylamide's substrates producing two different elastic modulus values (0.5 and 15 kPa). We measured a dose dependent increase in CD-44 relative expression in tumour cells cultured in a stiffer microenvironment. These findings highlight a crucial connection between the mechanical properties of the cell's surroundings and the post-radiotherapy expression of surface receptors.

Simple summaryStereotactic body radiotherapy (SBRT) of 35–36.25 Gy in five fractions with the CyberKnife System yields excellent control with low toxicity in low–intermediate-risk prostate cancer patients. We found no differences in biochemical control and overall survival in relation to dose. There were no significant differences in toxicity or quality of life between the two groups.AimsStereotactic body radiotherapy (SBRT) is an emerging therapeutic approach for low- and intermediate-risk prostate cancer. We present retrospective data on biochemical control, toxicity, and quality of life of CyPro Trial.Materials and methodsA total of 122 patients with low- and intermediate-risk prostate cancer were treated with the CyberKnife System at a dose of 35 Gy or 36.25 Gy in five fractions. Biochemical failure (BF)/biochemical disease-free survival (bDFS) was defined using the Phoenix method (nadir + 2 ng/ml). Acute/late rectal and urinary toxicities were assessed by the Radiation Therapy Oncology Group (RTOG) toxicity scale. Quality of life (QoL) was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and PR25. International Erectile Function Index-5 (IIEF5) and International Prostate Symptom Score (IPSS) questionnaires were administered at baseline, every 3 months after treatment during the first years, and then at 24 months and 36 months.ResultsThe 1-, 2-, and 5-year DFS rates were 92.9%, 92.9%, and 92.3%, respectively, while the 1-, 2-, and 5-year bDFS rates were 100%, 100%, and 95.7%, respectively. With regard to risk groups or doses, no statistically significant differences were found in terms of DFS or bDFS. Grade 2 urinary toxicity was acute in 10% and delayed in 2% of patients. No Grade 3 acute and late urinary toxicity was observed. Grade 2 rectal toxicity was acute in 8% and late in 1% of patients. No Grade 3–4 acute and late rectal toxicity was observed. Grade 2 acute toxicity appeared higher in the high-dose group (20% in the 36.25-Gy group versus 3% in the 35-Gy group) but was not statistically significant.ConclusionOur study confirms that SBRT of 35–36.25 Gy in five fractions with the CyberKnife System produces excellent control with low toxicity in patients with low–intermediate-risk prostate cancer. We found no dose-related differences in biochemical control and overall survival. Further confirmation of these results is awaited through the prospective phase of this study, which is still ongoing.

Tumor ablation is included in several major cancer therapy guidelines. One technical challenge of percutaneous ablation is targeting and verification of complete treatment, which is prone to operator variabilities and human imperfections and are directly related to successful outcomes, risk for residual unablated tumor and local progression. The use of “Prediction Ablation Volume Software” may help the operating Interventional Radiologist to better plan, deliver, and verify before the ablation, via virtual treatment zones fused to target tumor. Fused and superimposed images provide 3-dimensional information from different timepoints, just when that information is most useful. The aim of this study is to evaluate the technical success and efficacy of an ablation treatment flowchart provided by a cone beam computed tomography (CBCT) “Prediction Ablation Volume Software.” This is a single-center retrospective study. From April 2021 to January 2022, 29 nonconsecutive evaluable patients with 32 lesions underwent liver ablation with Prediction Ablation Volume Software. Each patient was discussed in a multidisciplinary tumor board and underwent an enhanced computed tomography or magnetic resonance imaging approximately 1 month before the procedure, as well as ∼1 month after. Technical success was defined as treatment of the tumor according to the protocol, covered completely by the Prediction Ablation Volume. Technical efficacy was defined as assessment of complete ablation of the target tumor at imaging follow up (∼1 month). Technical success, technical efficacy, and procedural factors were studied. Technical success was achieved in 30 of 32 liver lesions (94%), measuring 20 mm mean maximum diameter. The antenna was repositioned in 16 of 30 (53%) evaluable target lesions. Residual tumor was detected at 1 month imaging follow up in only 4 of 30 (13%) of the treated lesion. Technical efficacy was of 87% in this retrospective description of our process. The implementation of a CBCT Prediction Ablation Volume Software and flowchart for the treatment of liver malignancies altered the procedure, and demonstrated high technical success and efficacy. Such tools are potentially useful for procedural prediction and verification of ablation.

Biliary tract cancer (BTC) is an aggressive tumor characterized by a poor prognosis. In the latest years, targetable genetic alterations have been discovered in BTC patients, leading to the approval of new targeted therapies. Liquid biopsy, which is a non-invasive method for detecting tumor biomarkers from fluid samples, is a useful tool for diagnosis and molecular characterization, but also for prognosis assessment and monitoring of treatment response. In this review, recent works on liquid biopsy in BTC patients were analyzed, focusing on some relevant aspects for clinical use and trying to depict the future role of this technique. Moreover, differences between plasma and bile samples were pointed out, in light of the peculiar biology of BTC and the possibility of using bile as an alternative source of cell-free DNA (cfDNA) for genomic analysis. In the era of precision oncology, the increasing adoption of liquid biopsy in BTC patients will certainly improve the management of this disease.

Vertebral fractures are the most frequent fractures associated with osteoporosis. Thus far, there are no reported cases in literature analyzing intervertebral bleeding as a result of an osteoporotic vertebral fracture. The authors report a case of an 85-year-old woman in hemorrhagic shock for an unusual vertebral fracture causing a massive bleeding, which was contained by the vertebral ligament system inside the body of L4, treated with an endovascular approach. Since there are no guidelines for a treatment for the case mentioned above or similar, our aim is to describe a possible approach to a potentially life-threatening rare event.

The microenvironment of breast cancer actively participates in tumorigenesis and cancer progression. The changes observed in the architecture of the extracellular matrix initiate an oncogene-mediated cell reprogramming, that leads to a massive triggering of YAP nuclear entry, and, therefore, to cancer cell proliferation, invasion and probably to increased radiation-resistance. However, it is not yet fully understood how radiotherapy regulates the expression and subcellular localization of YAP in breast cancer cells experiencing different microenvironmental stiffnesses. To elucidate the role of extracellular matrix stiffness and ionizing radiations on YAP regulation, we explored the behaviour of two different mammary cell lines, a normal epithelial cell line (MCF10A) and a highly aggressive and invasive adenocarcinoma cell line (MDA-MB-231) interacting with polyacrylamide substrates mimicking the mechanics of both normal and tumour tissues (∼1 and ∼13 kPa). We report that X-ray radiation affected in a significant way the levels of YAP expression, density, and localization in both cell lines. After 24 h, MCF10A and MDA-MB-231 increased the expression level of YAP in both nucleus and cytoplasm in a dose dependent manner and particularly on the stiffer substrates. After 72 h, MCF10A reduced mostly the YAP expression in the cytoplasm, whereas it remained high in the nucleus of cells on stiffer substrates. Tumour cells continued to exhibit higher levels of YAP expression, especially in the cytoplasmic compartment, as indicated by the reduction of nuclear/cytoplasmic ratio of total YAP. Then, we investigated the existence of a correlation between YAP localization and the expression of the nuclear envelope protein lamin A/C, considering its key role in modulating nuclear deformability and changes in YAP shuttling phenomena. As supposed, we found that the effects of radiation on YAP nucleus/cytoplasmic expression ratio, increasing in healthy cells and decreasing in tumour ones, were accompanied by lower and higher lamin A/C levels in MCF10A and MDA-MB-231 cells, respectively. These findings point to obtain a deeper knowledge of the role of the extracellular matrix and the effects of X-rays on YAP and lamin A/C expression that can be used in the design of doses and timing of radiation therapy.

Traditionally, lymph node metastases (LNM) evaluation is essential to the staging of colon cancer patients according to the TNM (tumor–node–metastasis) system. However, in recent years evidence has accumulated regarding the role of emerging pathological features, which could significantly impact the prognosis of colorectal cancer patients. Lymph Node Ratio (LNR) and Log Odds of Positive Lymph Nodes (LODDS) have been shown to predict patients’ prognosis more accurately than traditional nodal staging and it has been suggested that their implementation in existing classification could help stratify further patients with overlapping TNM stage. Tumor deposits (TD) are currently factored within the N1c category of the TNM classification in the absence of lymph node metastases. However, studies have shown that presence of TDs can affect patients’ survival regardless of LNM. Moreover, evidence suggest that presence of TDs should not be evaluated as dichotomic but rather as a quantitative variable. Extranodal extension (ENE) has been shown to correlate with presence of other adverse prognostic features and to impact survival of colorectal cancer patients. In this review we will describe current staging systems and prognostic/predictive factors in colorectal cancer and elaborate on available evidence supporting the implementation of LNR/LODDS, TDs and ENE evaluation in existing classification to improve prognosis estimation and patient selection for adjuvant treatment.

An adequate and balanced diet is fundamental in preserving the health of astronauts from several space-induced diseases. Therefore, the integration of a diet with fresh food, rich in bioactive compounds such as microgreens produced directly onboard, may be useful in space for human nutrition. However, ionizing radiation (IR) in space represents a significant hindrance for organisms, with potential critical outcomes on plant morpho-anatomical, eco-physiological, and biochemical aspects, depending on the plant and IR features (e.g., species, developmental stage, IR dose, and type). In this study, we analyzed the effect of different doses of X-rays (0-control, 0.3, 1, 10, 20, and 30 Gy) on the morpho-anatomical and nutritional traits of microgreens of Brassica rapa L., irradiated at the stage of germinated seeds. After the irradiation, microgreens were cultivated in controlled conditions. At harvest, the morpho-biometric traits were analyzed, along with the leaf functional anatomical traits and the phytochemical content of the aboveground biomass. The results showed that X-ray exposure does not induce detrimental effects on growth, while it stimulates the production of antioxidants, improving plant defense and nutritional value. The overall results support the idea of using this species in space as a supplemental functional food.

Surface brachytherapy (BT) lacks standard quality assurance (QA) protocols. Commercially available treatment planning systems (TPSs) are based on a dose calculation formalism that assumes the patient is made of water, resulting in potential deviations between planned and delivered doses. Here, a method for treatment plan verification for skin surface BT is reported. Chips of thermoluminescent dosimeters (TLDs) were used for dose point measurements. High-dose-rate treatments were simulated and delivered through a custom-flap applicator provided with four fixed catheters to guide the Iridium-192 (Ir-192) source by way of a remote afterloading system. A flat water-equivalent phantom was used to simulate patient skin. Elekta TPS Oncentra Brachy was used for planning. TLDs were calibrated to Ir-192 through an indirect method of linear interpolation between calibration factors (CFs) measured for 250 kV X-rays, Cesium-137, and Cobalt-60. Subsequently, plans were designed and delivered to test the reproducibility of the irradiation set-up and to make comparisons between planned and delivered dose. The obtained CF for Ir-192 was (4.96 ± 0.25) μC/Gy. Deviations between measured and TPS calculated doses for multi-catheter treatment configuration ranged from −8.4% to 13.3% with an average of 0.6%. TLDs could be included in clinical practice for QA in skin BT with a customized flap applicator.

Immunotherapy has recently become a major treatment modality for several types of solid tumours, achieving remarkable and long-lasting remissions. In metastatic colorectal cancer patients (mCRC), immune checkpoint inhibitors (ICIs) were found to be effective as treatment for deficient mismatch repair (dMMR)/ microsatellite instability high (MSI-H) tumours and received regulatory approval for this indication. However, mCRC is a complex disease and dMMR/MSI-H tumours represent a minority of the cases; therefore, new strategies are needed to extend the benefits of immunotherapy to a larger population of patients. This review explores the immunological differences between dMMR/MSI-H and proficient mismatch repair (pMMR)/ microsatellite instability low (MSI-L) tumours, focuses on new proposed biomarkers to predict response to immunotherapy and illustrates results reported from the main clinical trials with immunotherapeutic agents in CRC, addressing the most promising approaches being currently developed.

In recent years, stereotactic body radiation therapy (SBRT) has gained popularity among clinical methods for the treatment of medium and low risk prostate cancer (PCa), mainly as an alternative to surgery. The hypo-fractionated regimen allows the administration of high doses of radiation in a small number of fractions; such a fractionation is possible by exploiting the different intrinsic prostate radiosensitivity compared with the surrounding healthy tissues. In addition, SBRT treatment guaranteed a better quality of life compared with surgery, avoiding risks, aftermaths, and possible complications. At present, most stereotactic prostate treatments are performed with the CyberKnife (CK) system, which is an accelerator exclusively dedicated for stereotaxis and it is not widely spread in every radiotherapy centre like a classic linear accelerator (LINAC). To be fair, a stereotactic treatment is achievable also by using a LINAC through Volumetric Modulated Arc Therapy (VMAT), but some precautions must be taken. The aim of this work is to carry out a dosimetric comparison between these two methodologies. In order to pursue such a goal, two groups of patients were selected at Instituto Nazionale Tumori—IRCCS Fondazione G. Pascale: the first group consisting of ten patients previously treated with a SBRT performed with CK; the second one was composed of ten patients who received a hypo-fractionated VMAT treatment and replanned in VMAT-SBRT flattening filter free mode (FFF). The two SBRT techniques were rescaled at the same target coverage and compared by normal tissue sparing, dose distribution parameters and delivery time. All organs at risk (OAR) constraints were achieved by both platforms. CK exhibits higher performances in terms of dose delivery; nevertheless, the general satisfying dosimetric results and the significantly shorter delivery time make VMAT-FFF an attractive and reasonable alternative SBRT technique for the treatment of localized prostate cancer.

A large body of literature has demonstrated that the mechanical properties of microenvironment have a key role in regulating cancer cell adhesion, motility, and invasion. In this work, we have introduced two additional parameters, named cell trajectory extension and area traveled by cell, to describe the tendency of normal tissue and metastatic cancer cells to move in a directional way when they interact with physio-pathological substrates, characterized by stiffnesses of 1–13 kPa, before and after treatment with 2 doses of X-rays (2 and 10 Gy). We interpreted these data by evaluating also the impact of substrate stiffness on 2 morphological parameters which indicate not only the state of cell adhesion, but also cell polarization, prerequisite to directional movement, and the formation of protrusions over cell perimeters. We believe that a so wide analysis can give an efficient and easily readable overview of effects of radiation therapy on cell-ECM crosstalk when used as therapeutic agent.

This is an illustrated case about CT ventilation and perfusion in Covid patient.

Mobile sensor platforms such as Autonomous Underwater Vehicles (AUVs) and robotic surface vessels, combined with static moored sensors compose a diverse sensor network that is able to provide macroscopic environmental analysis tool for ocean researchers. Working as a cohesive networked unit, the static buoys are always online, and provide insight as to the time and locations where a federated, mobile robot team should be deployed to effectively perform large scale spatio-temporal sampling on demand. Such a system can provide pertinent in situ measurements to marine biologists whom can then advise policy makers on critical environmental issues. This poster presents recent field deployment activity of AUVs demonstrating the effectiveness of our embedded communication network infrastructure throughout southern California coastal waters. We also report on progress towards real-time, web-streaming data from the multiple sampling locations and mobile sensor platforms. Static monitoring sites included in this presentation detail the network nodes positioned at Redondo Beach and Marina Del Ray. One of the deployed mobile sensors highlighted here are autonomous Slocum gliders. These nodes operate in the open ocean for periods as long as one month. The gliders are connected to the network via a Freewave radio modem network composed of multiple coastal base-stations. This increases the efficiency of deployment missions by reducing operational expenses via reduced reliability on satellite phones for communication, as well as increasing the rate and amount of data that can be transferred. Another mobile sensor platform presented in this study are the autonomous robotic boats. These platforms are utilized for harbor and littoral zone studies, and are capable of performing multi-robot coordination while observing known communication constraints. All of these pieces fit together to present an overview of ongoing collaborative work to develop an autonomous, region-wide, coastal environmental observation and monitoring sensor network.

Cutaneous melanoma is a lethal disease, even when diagnosed in advanced stages. Although recent progress in biology and treatment has dramatically improved survival rates, new therapeutic approaches are still needed. Deregulation of epigenetics, which mainly controls DNA methylation status and chromatin remodeling, is implied not only in cancer initiation and progression, but also in resistance to antitumor drugs. Epigenetics in melanoma has been studied recently in both melanoma preclinical models and patient samples, highlighting its potential role in different phases of melanomagenesis, as well as in resistance to approved drugs such as immune checkpoint inhibitors and MAPK inhibitors. This review summarizes what is currently known about epigenetics in melanoma and dwells on the recognized and potential new targets for testing epigenetic drugs, alone or together with other agents, in advanced melanoma patients.

Selective embolization is the treatment of choice for traumatic renal pseudoaneurysm. The use of ethylene vinyl alcohol copolymer (EVOH) was recently described as an embolic agent in peripheral lesions. The aim of a good embolic agent is to: achieve rapid and effective embolization; reach and fill distal vasculature targeted for embolization; be easy to prepare and use. Moreover, it should be highly radiopaque, controllable during administration, biocompatible and cost-effective. EVOH is a non-adhesive embolic agent and its efficacy is independent from the coagulant status. The risk of non-targeted embolization should be reduced by the good radio-opacity of the embolic material that is injected under continuous fluoroscopy. Nevertheless, symptomatic EVOH migration was described. We report a unique case of embolization of a renal pseudoaneurysm and migration of EVOH in the urinary tract. Retrograde trans-urethral removal of the migrated embolic agent was successfully performed. Our case report indicates that EVOH may not be appropriate when a fistula with renal calyx is suspected, even if its migration in the urinary tract may be managed.

The paper addresses observability issues related to the general problem of single and multiple Autonomous Underwater Vehicle (AUV) localization using only range measurements. While an AUV is submerged, localization devices, such as Global Navigation Satellite Systems, are ineffective, due to the attenuation of electromagnetic waves. AUV localization based on dead reckoning techniques and the use of affordable motion sensor units is also not practical, due to divergence caused by sensor bias and drift. For these reasons, localization systems often build on trilateration algorithms that rely on the measurements of the ranges between an AUV and a set of fixed transponders using acoustic devices. Still, such solutions are often expensive, require cumbersome calibration procedures and only allow for AUV localization in an area that is defined by the geometrical arrangement of the transponders. A viable alternative for AUV localization that has recently come to the fore exploits the use of complementary information on the distance from the AUV to a single transponder, together with information provided by on-board resident motion sensors, such as, for example, depth, velocity and acceleration measurements. This concept can be extended to address the problem of relative localization between two AUVs equipped with acoustic sensors for inter-vehicle range measurements. Motivated by these developments, in this paper, we show that both the problems of absolute localization of a single vehicle and the relative localization of multiple vehicles can be treated using the same mathematical framework, and tailoring concepts of observability derived for nonlinear systems, we analyze how the performance in localization depends on the types of motion imparted to the AUVs. For this effect, we propose a well-defined observability metric and validate its usefulness, both in simulation and by carrying out experimental tests with a real marine vehicle during which the performance of an Extended Kalman Filter state observer is shown to depend on the types of motion imparted to the vehicle.

The paper presents an overview on the use of a behavior-based approach, namely the Null-Space-based Behavioral (NSB) approach, to control multi-robot systems in a wide application domain. The NSB approach has been recently developed to control the motion of generic robotic systems; it uses a projection mechanism to combine the multiple, prioritized, behaviors that compose the robotic mission so that the lower priority behaviors do not effect the higher priority ones. In this paper we describe how the NSB approach has been used to control different multi-robot systems (e.g., composed of wheeled and marine robots) to achieve missions such as formation control, entrapping/escorting of targets, control of mobile ad-hoc networks, flocking, border patrol and cooperative caging.

We studied left ventricular diastolic function by equilibrium gated radionuclide angiography in patients as follows: 75 with acute myocardial infarction (AMI), 35 with anterior or anteroseptal necrosis (Group A) and 40 with inferior, inferolateral, or posterior necrosis (Group I). The ejection fraction (EF) was lower in Group A than Group I (41.9 +/- 2.5 vs. 57.1 +/- 2.0%, p less than 0.001), as was peak diastolic filling rate normalized to end diastolic volume (PDFR-EDV/sec) (1.9 +/- 0.1 vs. 2.4 +/- 0.1 EDV/sec, p less than 0.05). PDFR normalized to stroke volume was similar in both groups. An excellent linear correlation was found between EF and PDFR-EDV/sec in the total study population. Isovolumic relaxation period (IRP) was beyond our upper normal value of 94 msec in 64% of patients and it was shorter in Group A than I (95.8 +/- 12.7 vs. 147.0 +/- 13.6 msec, p less than 0.05). The presence of shorter IRP in Group A than in I is probably a result of an earlier mitral valve opening as a consequence of higher left atrial pressure.