Late Reversal Research Articles

Early versus late reversal of diverting loop ileostomy in rectal cancer surgery: a multicentre randomized controlled trial

Diverting loop ileostomy has become routine in low anterior resection (LAR) for rectal cancer. The optimal time for stoma reversal is controversial. The aim of the present study was to compare the results after planned early (within 8–12 days) versus late (> 3 months) stoma reversal. The primary outcomes were morbidity and mortality, as measured by the Comprehensive Complication Index (CCI) within 30 days after stoma reversal, and the secondary outcomes were morbidity and mortality within 90 days after LAR. This was a multicentre trial including all patients scheduled for anterior low resection for rectal cancer with curative intent. Inclusion period was from April 2011 to December 2018. All patients were randomized 1:1 prior to surgery. Among 257 consecutive and eligible patients, a total of 214 patients were randomized: 107 patients to early stoma reversal and 107 to late reversal. A total of 68 patients were excluded for various reasons, and 146 patients completed the study, with 77 in the early reversal group and 69 in the late reversal group. The patients were asked to complete the Gastrointestinal Quality of Life Index before surgery (baseline) and at 6 and 12 months after LAR. Ostomy-related complications were evaluated by dedicated ostomy staff using the validated DET score. ClinicalTrials Identifier: NCT01865071. Fifty-three patients (69%) in the early reversal group and 60 patients (87%) in the late reversal group received the intended treatment. There were no significant differences in CCI within 90 days after index surgery with the LAR and within 30 days after stoma reversal between the two groups. There were no differences in patient-reported quality of life but significantly more stoma-related complications in the late reversal group. A total of 5 patients experienced anastomotic leakage (AL) after stoma reversal, 4 in the early reversal group and one in the late reversal group. Early and late stoma reversal showed similar outcomes in terms of overall complications and quality of life. The risk of developing anastomotic leakage after early ostomy reversal is a concern.

Outcomes of Early Versus Late Reversal in Patients with Loop Ileostomy Formation Secondary to Typhoid Perforation

Objective: To assess if there is significant risk associated with early reversal of stomas (less than 6 weeks) when compared to a delayed closure in the setting of a Tertiary Care Hospital in Karachi. Study design: Observational longitudinal study Study place and duration: Dow University, Karachi 6 months 1st April 2022 till 1st September 2022 Methods: Pre- and post-operative data were collected for 50 patients assigned to each group respectively. The parameters assessed were the American Society of Anesthesiologists (ASA) grade, Surgery duration, Post-operative and Overall Hospital Stay, Surgical and Medical complications and day of occurrence, Clavein-Dindo Classification, and mortality. Results: Significant variance in ASA Grade was noted between the two groups, P-Value=0.005 with a lower grade observed in patients who underwent early closure. The post-operative and total hospital stay showed significant variation, with P-values of 0.011 and 0.011, respectively for both outcomes. The incidence of post-operative complications was also significant with p-value=0.004. The median day at which post-operative complication occurred was 4.5 vs 3 days with a significant p-value of 0.038. Conclusions: Late closure is associated with a significantly higher risk of complications and a resultant greater length of hospital stay. Keywords: Ileostomy, stoma, intestinal perforation, and typhoid

Terminal Pleistocene human occupation of the upper Copper River basin, southern Alaska: Results of test excavations at Nataeł Na’

After decades of debate, the homeland of the First Americans is now generally understood to be northeast Asia; however, the process of Late Pleistocene peopling remains unresolved. As more archaeological sites south of the continental ice sheets are discovered that predate the opening of the interior “ice-free” corridor, interest in a coastal Pacific dispersal route has grown, and previously overlooked regions proximal to the Pacific coast have become a central focus of exploration efforts. The Copper River basin of southern Alaska is one such region. Here we present the results of 2019 archaeological excavations at Nataeł Na’, a buried and stratified archaeological site situated along the upper Copper River. The site contains a robust occupation dating to the late Younger Dryas climate reversal as well as an earlier occupation dating to the late Allerød interstadial. This discovery demonstrates that Pleistocene hunter-gatherers inhabited the Pacific basin of southern Alaska during the same time Clovis peoples inhabited temperate North America. The occupations at Nataeł Na’ join a growing body of evidence suggesting that the early inhabitants of eastern Beringia were geographically more widely dispersed than previously documented.

Modeling Equatorial F‐Region Ionospheric Instability Using a Regional Ionospheric Irregularity Model and WAM‐IPE

AbstractThis paper uses a regional simulation of plasma convective instability in the postsunset equatorial ionosphere together with a global atmosphere/ionosphere/plasmasphere GCM (WAM‐IPE) to forecast irregularities associated with equatorial spread F (ESF) for 1–2 hr after sunset. First, the regional simulation is initialized and forced using ionosphere state parameters derived from campaign data from the Jicamarca Radio Observatory and from empirical models. The irregularities produced by these simulations are found to be quantitatively similar to those observed. Next, the aforementioned state parameters are replaced with parameters from WAM‐IPE, and the resulting departures between the simulated and observed irregularities are noted. In one of five cases, the forecast failed to accurately predict ESF irregularities due to the late reversal of the zonal thermospheric winds. In four of five cases, significant differences between the observed and predicted prereversal enhancement (PRE) of the background vertical drifts resulted in degraded forecast accuracy. This highlights the need for improved PRE forecasting in the global‐scale model.

Stoma Reversal : A Restropective Study of 36 Cases at A Non-Government Hospital

Background : Formation of intestinal stoma is a common surgical practice. In this study, we aim to study the indications for stoma creation, complications of stomas, timing and methods of stoma reversal, reasons for any delays and post-reversal complications. Material and methods: This is a restropective study Charts of patients who underwent stoma creation and reversal over a 3 year period from January 2018 to December 2020 at Banghbandhu Memorial Hospital are included in this study. Results: A total of 49stomas were created out of which 36 were reversed. Overall pre-takedown complications were 26 % and post-takedown complications were 30% most of which were minor complications, not requiring major interventions. There was no significant difference in outcome due to early vs. late reversal, types of anesthesia or reversal technique. Conclusion: Reversal of temporary stomas can be done safely at an early date, with no demand of special anesthesia, requiring minimal access to the abdomen and with safe early discharge without expecting serious complications or readmissions. IAHS Medical Journal Vol 5(1), June 2022; 78-81

Threat reversal learning and avoidance habits in generalised anxiety disorder

Avoidance and heightened responses to perceived threats are key features of anxiety disorders. These disorders are characterised by inflexibility in dynamically updating behavioural and physiological responses to aversively conditioned cues or environmental contexts which are no longer objectively threatening, often manifesting in perseverative avoidance. However, less is known about how anxiety disorders might differ in adjusting to threat and safety shifts in the environment or how idiosyncratic avoidance responses are learned and persist. Twenty-eight patients with generalised anxiety disorder (GAD), without DSM co-morbidities, and 27 matched healthy controls were administered two previously established paradigms: Pavlovian threat reversal and shock avoidance habits through overtraining (assessed following devaluation with measures of perseverative responding). For both tasks we used subjective report scales and skin conductance responses (SCR). In the Pavlovian threat reversal task, patients with GAD showed a significantly overall higher SCR as well as a reduced differential SCR response compared to controls in the early but not late reversal phase. During the test of habitual avoidance responding, GAD patients did not differ from controls in task performance, habitual active avoidance responses during devaluation, or corresponding SCR during trials, but showed a trend toward more abstract confirmatory subjective justifications for continued avoidance following the task. GAD patients exhibited significantly greater skin conductance responses to signals of threat than controls, but did not exhibit the major deficits in reversal and safety signal learning shown previously by patients with OCD. Moreover, this patient group, again unlike OCD patients, did not show evidence of altered active avoidance learning or enhanced instrumental avoidance habits. Overall, these findings indicate no deficits in instrumental active avoidance or persistent avoidance habits, despite enhanced responses to Pavlovian threat cues in GAD. They suggest that GAD is characterised by passive, and not excessively rigid, avoidance styles.

I change my mind to get better: Process tracing-based microanalysis of food choice processes reveals differences between anorexia nervosa and bulimia nervosa during inpatient treatment

Food choice and its underlying processes is understudied in bulimia nervosa (BN) and anorexia nervosa (AN). Thus, we examined cognitive processes during food choice through mouse tracing in AN (n = 36) and BN (n = 27) undergoing inpatient treatment. Both patient groups and matched healthy controls (HC, n = 59) made 153 binary food choices before rating all foods on their liking and calorie density. Choice outcomes and corresponding mouse movements were modelled as a function of inpatient treatment stage in our analyses.Compared to patients with BN and HC, those with AN showed a clear calorie avoidance on most trials. Yet, mouse paths in AN patients early in treatment, revealed a late direction reversal (‘change of mind’, CoM) on high-calorie choices. AN patients later in treatment, by contrast, showed fewer CoM alongside more choices for – and liking of – high-calorie foods. Patients with BN showed more CoM trials during low-calorie choices and low-calorie choices were more frequent in patients later in treatment. Thus, relative to patients early in treatment, patients who are later in treatment show less of the overall group pattern of consistently choosing low-calorie food (AN) or high-calorie food (BN). Less cognitive regulation (fewer CoM trials) went along with higher liking for high-calorie foods in AN. These cross-sectional differences between AN early and late in treatment might reflect the formation of healthier habits. In addition, clear patient group differences suggest more specific treatment strategies.

Marine record of late-glacial readvance and last recession of Laurentide ice, inner Frobisher Bay, Baffin Island, Arctic Canada

The Cockburn Substage readvance marks the last major late-glacial advance of the northeast sector of the Laurentide Ice Sheet on Baffin Island. The causes of this abrupt, late reversal of retreat are still unclear, but greater chronological control may provide some insight. To date, the literature has focused on the large terminal moraines in the region, providing a date of readvance (circa 9.5–8.5 ka cal BP). In Frobisher Bay, the Cockburn Substage readvance and recession onshore are marked by a series of moraines spread over ∼20 km along the inner bay. Acoustic marine mapping reveals five distinct transverse ridges, morphologically suggestive of grounding-zone wedges, and two later fields of DeGeer moraines on the floor of the inner bay. These indicate that the style of ice retreat (beginning no later than 8.5 ka cal BP) changed over time from punctuated recession of a floating ice front (20 km over >680 years, with four pauses) to more regular tidewater ice-front retreat, reaching the head of the bay 900 years or more after withdrawal from the outer Cockburn limit. The established chronology for final recession in the region is based largely on radiocarbon dating of bulk shell samples and single shells of deposit-feeding molluscs, notably Portlandia arctica, affected by old carbon from carbonate-rich sediments. Sedimentary analysis and judicious sampling for 14C dating of glaciomarine and marine facies in seabed sediment cores enables development of a late- and post-glacial lithostratigraphy that indicates final withdrawal of ice from the drainage basin by 7 ka cal BP.

Effects of Laparoscopic Hartmann Reversal on Short-term Operative Outcomes Among Vietnamese Patients

Abstract Background The reestablishment of continuity after Hartmann operation is considered a major surgical procedure with high morbidity and mortality. The optimal interval time between the Hartman procedure and reversal is controversial. Our study aimed to evaluate the effectiveness of laparoscopic Hartmann reversal and to determine the optimal timing of operation. Methods All patients who underwent laparoscopic Hartmann reversal from 2008 to 2019 (11 years) at the University Medical Center (UMC) in Ho Chi Minh City were recruited and divided into 2 groups according to the interval time (≤ 4 or > 4 months). The short-term operative outcomes of these groups were compared. Results There were 66 patients who underwent laparoscopic Hartmann reversal (mean age: 63.2 years old); ∼ 77% of them had colorectal cancer, and 17% had complicated diverticular disease. The mortality rate, anastomotic leakage rate, and overall complication rate were 0%, 1.5%, and 13.2%, respectively. Early operation was performed in 36 patients, and late reversal in 28 patients. There was no difference in mortality, anastomotic leakage, operative complications, and hospital stay between the two groups. Conclusion Laparoscopic Hartmann reversal was effective with acceptable morbidity and mortality at the UMC. There was no observed impact of the interval time between the Hartmann procedure and laparoscopic Hartmann reversal on the short-term operative outcomes.

PIEZO1 and the mechanism of the long circulatory longevity of human red blood cells

Human red blood cells (RBCs) have a circulatory lifespan of about four months. Under constant oxidative and mechanical stress, but devoid of organelles and deprived of biosynthetic capacity for protein renewal, RBCs undergo substantial homeostatic changes, progressive densification followed by late density reversal among others, changes assumed to have been harnessed by evolution to sustain the rheological competence of the RBCs for as long as possible. The unknown mechanisms by which this is achieved are the subject of this investigation. Each RBC traverses capillaries between 1000 and 2000 times per day, roughly one transit per minute. A dedicated Lifespan model of RBC homeostasis was developed as an extension of the RCM introduced in the previous paper to explore the cumulative patterns predicted for repetitive capillary transits over a standardized lifespan period of 120 days, using experimental data to constrain the range of acceptable model outcomes. Capillary transits were simulated by periods of elevated cell/medium volume ratios and by transient deformation-induced permeability changes attributed to PIEZO1 channel mediation as outlined in the previous paper. The first unexpected finding was that quantal density changes generated during single capillary transits cease accumulating after a few days and cannot account for the observed progressive densification of RBCs on their own, thus ruling out the quantal hypothesis. The second unexpected finding was that the documented patterns of RBC densification and late reversal could only be emulated by the implementation of a strict time-course of decay in the activities of the calcium and Na/K pumps, suggestive of a selective mechanism enabling the extended longevity of RBCs. The densification pattern over most of the circulatory lifespan was determined by calcium pump decay whereas late density reversal was shaped by the pattern of Na/K pump decay. A third finding was that both quantal changes and pump-decay regimes were necessary to account for the documented lifespan pattern, neither sufficient on their own. A fourth new finding revealed that RBCs exposed to levels of PIEZO1-medited calcium permeation above certain thresholds in the circulation could develop a pattern of early or late hyperdense collapse followed by delayed density reversal. When tested over much reduced lifespan periods the results reproduced the known circulatory fate of irreversible sickle cells, the cell subpopulation responsible for vaso-occlusion and for most of the clinical manifestations of sickle cell disease. Analysis of the results provided an insightful new understanding of the mechanisms driving the changes in RBC homeostasis during circulatory aging in health and disease.

The safety of early versus late ileostomy reversal after low anterior rectal resection: a retrospective study in 47 patients

BackgroundThis study aimed to clarify the safety of early closure in diverting ileostomy with lower anterior rectal-cancer resection.MethodsWe retrospectively reviewed consecutive 47 patients who underwent diverting ileostomy with lower rectal-cancer resection between May 2009 and October 2017. The results of the stoma closure were compared between patients who underwent stoma closure within 90 days (early closure [EC] group) and those who underwent late closure (LC group; closure after 90 days). Because of the small sample size, the frequency of severe complications post closure was analyzed.ResultsAmong 47 patients, 29 were in the EC group. Postoperative complications occurred in 48.3% (14/29) and 27.8% (5/18) of patients in the EC and LC groups, respectively. This difference was due to minor complications (Clavien-Dindo Classification I/II), such as superficial incisional surgical site infections (n=5) in the EC group. The rate of severe complications (Clavien-Dindo Classification ≥ III) was similar between the groups (20.7% vs. 16.7%, p=1, Fisher’s exact test).ConclusionsNo association was observed between the time of closure and development of major complications; however, there was an increased likelihood of minor complications after EC. This study provides a basis on which future treatment guidelines for early stoma closure may be developed without affecting patient quality of life.

Stoma Formation in Crohn’s Disease and the Likelihood of Antidepressant Use: A Population-Based Cohort Study

The impact of a temporary or permanent stoma on mental health in Crohn's Disease (CD) is unknown. The aim was to examine the association between intestinal surgery and stoma formation and subsequent antidepressant medication (ADM) use. Using the Clinical Practice Research Datalink, we identified individuals with CD who underwent intestinal surgery between 1998-2018. We excluded individuals with a prescription for an ADM in the 6 months before surgery. Individuals were stratified into three groups: no stoma, temporary stoma, and permanent stoma. We used Kaplan-Meier curves to examine initiation of ADM after intestinal surgery and Cox regression to identify risk factors for ADM use after intestinal surgery. We identified 1,272 cases of CD undergoing their first intestinal surgery. Of these, 871 (68.5%) had no stoma, 191 (15.0%) had a temporary stoma and 210 (16.5%) had a permanent stoma. The 10-year cumulative incidence of ADM use was 26.4%, 33.4% and 37.3% respectively. Individuals with a permanent stoma were 71% more likely to receive an ADM than those with no stoma (HR 1.71, 95% CI 1.20-2.44). Individuals with a temporary stoma reversed within 12 months had a similar likelihood of ADM use to those without stoma formation (HR 0.99, 95% CI 0.64-1.53) whereas temporary stoma formation with late reversal after 12 months was associated with significantly greater likelihood of ADM use (HR 1.85, 95% CI 1.15-2.96). Permanent stomas and temporary stomas with late reversal surgery are associated with increased ADM use after intestinal surgery, likely associated with increased anxiety and depression.

Calling an Audible: COVID-19 and Competitive Sports.

Calling an Audible: COVID-19 and Competitive Sports.

Persistent plaques after release from treatment in slit-skin smear negative leprosy patients: Wait and watch or adopt a proactive approach?

A subset of leprosy patients has clinical and histopathological activity in the form of persistent plaques and granulomas after completion of multidrug therapy (MDT) which can have significant impact on their quality of life. In the absence of clear guidelines regarding management of such patients, majority of the times they are treated either as late reversal reaction with corticosteroids or no active treatment is offered. We observed 11 patients of leprosy with persistent plaques after completing the 6/12-months MDT who were treated favorably with minocycline 100 mg once daily for 16 weeks. Complete clinical resolution was observed in 9/11 patients while two patients had partial improvement. Histopathological improvement in the form of disappearance of granulomas corroborated with the clinical improvement. All the patients tolerated the treatment well and hyperpigmentation was the only adverse effect noted. Minocycline may be considered as a useful and well tolerated therapeutic option for this subset of leprosy patients due to its immune modulatory and anti-inflammatory effects.

Oncoepidemiological situation of sarcomas in Kazakhstan

Abstract Background Sarcoma is a malignant tumor of soft tissues and bones. They make up 1% of all malignant tumors in adults and 15% in children. More common in men 1.1: 1. By age: 20.7% - up to 40 years old, 27.6% - 40-60 years old and 51.7% over 60 years old. In 2018, in the Kazakhstan, malignant tumor of connective and soft tissues of 444 (1.4%) cases was registered and ranks 19th in the structure of cancer, bones and articular cartilage 188 (0.6%), takes 22nd place. Of these, with sore cases, bone sarcomas were recorded - 12.7%, soft tissues - 9.5%. The mortality rate from soft tissue sarcoma is -177 (1.2%) people, bone sarcoma - 85 (0.6%) people. Five-year survival of patients from soft tissue sarcomas is 53.8%, from bone sarcomas - 67.3%. Methods from 2015 to 2019, 1,068 patients with malignant tumor of bones and articular cartilage, 963 patients with malignant tumor of connective and soft tissues addmited to KazNIIOiR. Of these, 225 patients underwent organ-sparing surgeries - endoprosthesis replacement of limbs. Results In Kazakhstan over the past 5 years there has been an increase in the incidence of sarcomas of bones and soft tissues. Conclusions in comparison with previous years, there is an increase in the incidence of malignant tumor of bones and articular cartilage, connective and soft tissues, and an increase in mortality from tumor of bones and articular cartilage in men by 16.7%, in women by 50%. Late reversal of patients at the IV stage and a high proportion posthumously recorded in patients with maliganan tumors. Key messages Purpose: Assessment of the epidemiological situation and incidence of sarcomas of the bones and soft tissues in Kazakhstan. Out of 25 localizations of cancer, detection is worsened during professional examinations in 10 localizations, of which bones and articular cartilage, connective and other soft tissues.

The feasibility and safety of early ileostomy reversal: a systematic review and meta-analysis.

Recent evidence supports the safety of early reversal of a temporary stoma, within 14 days of construction. The aim of this systematic review and meta-analysis was to evaluate the post-operative morbidity and overall feasibility of early stoma reversal. Medline and Cochrane databases were searched for studies up to June 2019 that investigated the outcomes of early stoma reversal (EC, defined as closure ≤14 days from the index operation) versus late stoma reversal (LC, ≥8 weeks from the index operation). Meta-analysis was performed on the respective rates of post-operative morbidity, anastomotic leak, wound infection, bleeding, sepsis, small bowel obstruction and ileus. Nine studies were included (667 patients analysed). Meta-analysis showed no significant difference in the post-operative morbidity rate, anastomotic leak rate, rates of small bowel obstruction, bleeding and ileus between EC and LC. However, the wound infection rate was significantly higher after EC than LC; relative difference 0.10 (95% confidence interval 0.00-0.19, P = 0.047). The stoma-related complication rate was significantly higher after LC than EC; relative difference -0.28 (95% confidence interval -0.45 to -0.11, P = 0.001). The concept of early stoma reversal is appealing, and this meta-analysis confirms the safety of early stoma closure with an associated reduction in stoma-related complications despite higher wound infection rates. However, the results need to be interpreted with caution due to the heterogeneity of the studies included, especially in respect of the definition of complications that were used. Further well-designed prospective studies are required prior to confident adoption of early stoma closure into clinical practice.

Comments in response to report on 'Late reversal reaction with resistant Mycobacterium leprae: an emerging paradigm'.

Comments in response to report on 'Late reversal reaction with resistant Mycobacterium leprae: an emerging paradigm'.

Современная диагностика и лечение аллергического ринита у детей в Киргизской Республике

The aim of the study was to study the detection and treatment of allergic rhinitis in children in the Kyrgyz Republic. A prospective study included 79 children with suspected allergic rhinitis. It was found that 79 patients were diagnosed with allergic rhinitis using an adapted questionnaire. Late reversibility, the duration of the disease on average 3 years from the onset of the first symptoms, and a severe course, indicate a diagnosis of the disease. In allergic rhinitis intermittent flow, sensitization to pollen of cereals and trees predominates, and in persistent, weed, domestic, and epidermal allergens are noted. The effectiveness of subcutaneous and sublingual allergen-specific immunotherapy methods in children was evaluated.

Верхнедевонские отложения (франский ярус) северо-запада Русской платформы: палеомагнитные данные

Paleomagnetic determinations for the Devonian strata of the Main Devonian Field, available in the international paleomagnetic data base, do not make it possible to construct both detailed magnetostratigraphic scales and reliable trajectories of the apparent polar wander path of the paleomagnetic pole. This is primarily due to the insufficient amount of data that determine modern reliability criteria. Obtaining more complete series of reliable paleomagnetic determinations is one of the important tasks of paleomagnetic studies. The paper presents new paleomagnetic determinations from a collection of rocks of the Frasnian stage of the Upper Devonian (Ilmen and Bureg Beds of the Semiluky Formation), sampled on the southern shore of Lake Ilmen, east of the village. Korostyn in 2009. Magnetomineralogical studies were carried out to determine the magnetic minerals of carriers of natural remanent magnetization. Three characteristic components of natural remanent magnetization have been identified. Two components correspond to the Late Paleozoic magnetization reversal (in the Carboniferous and Permian times). The third, bipolar component of the Frasnian age passes the reverse polarity test of the geomagnetic field.. The obtained position of the paleomagnetic pole by the bipolar component of the natural remanent magnetization is consistent with the available data on the section of the Late Upper Devonian of the Main Devonian Field.

P645 Familial restrictive cardiomyopathy and Noonan"s syndrome: a rare association

Abstract Background Noonan syndrome is a rare genetic disorder. Typical cardiac involvement include pulmonary stenosis and hypertrophic cardiomyopathy. We present the association of Noonan syndrome with familial non-hypertrophic cardiomyopathy with haemodynamic features of restrictive physiology. Case description. A 30-year old male patient presented to the outpatient clinic with clinical symptoms of heart failure which was slowly progressive since age 20. He was found to have features of restrictive cardiomyopathy aged 12 years at the time when his mother was diagnosed with Noonan syndrome and restrictive cardiomyopathy. On examination, his 1st and 2nd heart sounds were normal, however 3rd heart sound was present. Pulse was regular, 75 per minute, BP 110/70 mmHg. Chest was clear and saturation 98%. Echocardiography showed small left ventricle (LV) with preserved ejection fraction (EF), borderline LV wall thickness (10-11 mm), restrictive filling pattern with mitral valve E/A ratio 4.2 and deceleration time 68 ms; dilated both atria; and pulmonary artery systolic pressure of 37 mmHg (Figure, panels A-C; F). Prominent late diastolic reversal flow was noted in hepatic veins (Panel D). LV longitudinal strain was borderline in absolute value (-18%) however demonstrated ‘apical sparing’ pattern (Panel E). The right ventricle was small in size with mild hypertrophy and dynamic function, but normal flow through pulmonary valve. Prominent diastolic reversal flow was also noted in superior vena cava. Cardiac magnetic resonance confirmed echocardiographic findings and additionally demonstrated prominent trabeculations and myocardial crypts in the LV, small pericardial effusion; no signs of amyloidosis, myocardial infarction, infiltration or fibrosis. Right heart catheterisation showed borderline pulmonary hypertension with a mean pressure of 25 mmHg, raised pulmonary artery wedge pressure 18 mmHg, normal pulmonary vascular resistance 1.9 WU, and a ‘square root sign’ (Panel G). Patient underwent cardiopulmonary exercise testing, he stopped after 9 mins of Bruce protocol due to fatigue, reaching the Peak VO2 of 21.1ml/kg/min (49% of predicted value). No ST changes or arrhythmic events were noted. Patient was diagnosed with primary (non-infiltrative) familial restrictive cardiomyopathy and discussed at multidisciplinary team meeting with recommendation of close follow-up for timing for heart transplantation. Meanwhile he was encouraged to continue treatment with ramipril and start regular physical activity. Discussion There are only few reports describing familial non-hypertrophic cardiomyopathy in patients with Noonan syndrome and none in their family members. We review typical clinical and diagnostic features of restrictive cardiomyopathy involving both ventricles and raise awareness of clinicians of primary familial restrictive cardiomyopathy as a possible cardiac manifestation in patients with Noonan syndrome and their immediate family members. Abstract P645 Figure.