High grade serous ovarian cancer (“HGSOC”) is the seventh most common cancer worldwide among women. The disease has no unique symptoms and often women are diagnosed in advance stages. The World Health Organization estimates that 225,500 women are diagnosed and 140,200 will die of this disease per year. In the United States, the 5-year survival rate is 43%, and 85% of all HGSOC patients experience recurrence despite aggressive treatment. More efficacious drug combination treatments are needed. Recently it was found that platinum drugs are inactivated in dimethyl sulfoxide (DMSO). Thus drug discovery platforms that use it as a solvent are not able to study platinum drugs in combination with other drugs easily. Advances in Echo technology at the National Center for Advancing Translational Sciences (NCATS) enabled acoustic transfer of platinum drugs in aqueous solutions. This allows us to find novel small molecule/platinum drug combinations that can be tested in clinical trials.We ran single-agent dose-response experiments to correctly estimate the dose-ranges needed for the matrix screens utilizing the OVCAR8 human carcinoma cell line. Then, we conducted our pilot matrix screen with compounds that are commonly combined with cisplatin for HGSOC treatment. Lastly, we spotted cisplatin against the Mechanism Interrogation PlatE drug library to identify novel combinations for clinical use against HGSOC. Compounds that show synergistic cell killing will give insight into novel drug combinations to treat HGSOC.Several synergistic and antagonistic effects were found. These results were refined with smaller-scale screening and tested in other HGSOC cell lines.The novel combinations discovered will allow chemotherapy patients to receive lower dosages of platinum drugs while maintaining or improving efficacy of cytotoxicity of cancer cells. This will help alleviate the side-effects of platinum drugs experienced by HGSOC patients.


As Congress considers renewing the Acute Hospital Care At Home (AHCaH) waiver, which provides a full hospital payment for Hospital at Home (HaH) care, evaluating uncertainty around the future of HaH payment is critical. Our qualitative study explored HaH leaders’ experiences with implementing HaH  from 14 new and pre-existing programs across the U.S. We conducted semi-structured interviews with HaH programs diverse by size, urbanicity, and geography. We analyzed transcripts using a thematic approach. Participants across settings and regions wanted greater clarity about the waiver’s future. Lack of clarity affected staffing (nurses reluctant to take temporary jobs) and investment in establishing programs . Programs adapted to uncertainty in multiple ways: 1) operating parallel waiver and non-waiver programs; 2) seeking to determine/ calculate the HaH value for their institution; 3) determining which patients would benefit most from HaH; and 4) seeking additional health system financing options beyond the CMS reimbursement (new programs) or relying on existing contracts with payers (existing programs). Implementing HaH is a complex and resource intensive process. Greater clarity from CMS regarding the waiver’s future state will encourage programs to invest the resources that they need to establish their programs long-term. Waiver extension/ permanence would also enable programs to develop and test measures of value, making rigorous evaluations possible to optimize different HaH components.


Clustering algorithms are commonly used to identify disease clusters. New Clustering algorithms are benchmarked on synthetic data to assess their accuracy. These datasets lack the complexities of real electronic health record (EHR) producing a partial assessment of the algorithm. We developed a synthetic EHR cluster generator for benchmarking clustering algorithms.We have created a synthetic EHR cluster generator, clustEHR, based on Synthea, a synthetic EHR generator that produces datasets (with parameterized noise and cluster separation) of known clusters and with clinically relevant patient outcomes. We evaluated clustEHR by generating multiple datasets of variable cluster separation and percentage of noise variables to reflect easy and hard clustering problems. We used a linear model to assess the relationship between these parameters and cluster problem difficulty. K-means accuracy was used as a proxy to measure cluster problem difficulty.We have developed a tool for generating synthetic EHR cluster data with clinically relevant outcomes based on the rate of decline of medical observations (e.g. blood pressure). The following parameters are supported: a) number of clusters, b) number of patients in each cluster, c) number and data type of features, d) separation through defining clusters as either diseases such as COPD or dementia (high separability) or inter-disease conditions such as emphysema and chronic bronchitis within COPD (low separability), and e) noise variables through identifying variables not predictive of true cluster outcomes random forest feature importance metric. We show that high cluster separation significantly increases k-means accuracy (coefficient of 0.33). Smaller percent of noise variables increase accuracy though not significantly (coefficient 0.42).ClustEHR offers realistic mixed data types as well as outcomes which are frequently used to evaluate clusters when subtyping diseases. The evaluating results suggest that the difficulty of the cluster data can be user determined. The tool can be used to create realistic datasets for evaluating clustering approaches.


Psychiatric illnesses are common among older adults and are associated with increased mortality and physical comorbidities. It is suggested that patients with frailty have a higher prevalence of depressive symptoms. (1) The eFI (electronic Frailty Index) is a tool used to assess the severity of frailty in elderly frail patients using a cumulative deficit model based on routine interactions with their GP.Patients were selected for annual frailty assessments by searching the electronic clinical system (SystmOne) using the eFI tool. Patients were assessed using the Comprehensive Geriatric Assessment (CGA) framework. In addition, all patients were screened for coexisting anxiety and depression using the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) questionnaire.Of the 118 patients who ranged from mild to severe frailty, we found there was a positive correlation of the frailty severity eFI scores with increased rates of anxiety and depression evidenced by higher scores on the PHQ-9 and GAD-7 scoring tools. We found a positive correlation of the eFI with the PHQ-9 depression scores of (r = 0.819 p < 0.001). Within the same data set, we found correlation coefficients of eFI and anxiety GAD-7 scores (r = 0.651 p < 0.001). Increasing frailty was found to be associated with a higher rate of depression and anxiety.We found in this study higher (eFI) electronic frailty indices are associated with higher rates of anxiety and depression. We would recommend annual frailty assessments in patients with high electronic frailty indices and this should include screening for mental health deterioration. Early detection of deterioration will enable patient centered supportive measures and targeted treatment strategies. Health maintenance programs should ensure patient centered holistic assessment of both physical and mental health needs for early identification to avoid deterioration of both physical and mental health.


A 55-year-old female presented with bilateral lower limb swelling and facial swelling along with a decreased frequency of micturition. Baseline investigations revealed an elevated serum creatinine and blood urea nitrogen. Subsequent investigations revealed a positive antinuclear antibodies (ANA) +++  and positive anti-double-stranded DNA (dsDNA) testing. A detailed ophthalmic evaluation was performed. Her visual acuity was 6/36 improving to 6/18 in either eye. The near vision was found to be N36 without any further improvement. A dilated fundus examination revealed multiple yellowish lesions throughout the posterior pole consistent with pockets of subretinal fluid in the right eye. A swept-source optical coherence tomography (OCT) was performed that revealed the presence of fluid in both the intraretinal and subretinal spaces. A bacillary layer detachment, with the accumulation of fluid in the intraretinal space, was noted. Similar fundus findings were seen in the left eye. A decision was made to employ plasmapheresis (PLEX) along with her routine thrice-weekly hemodialysis. Additionally, the systemic steroids were continued. At her third follow-up (day 22), her vision had improved to 6/9 unaided bilaterally and to N6 with the appropriate correction. There was a near-complete regression of the exudative retinal detachments bilaterally with pigmentary changes. The OCT scans revealed significant regression of the serous retinal and retinal pigment epithelium (RPE) detachments with a thin rim of residual subretinal fluid. Fundus examination and OCT studies established the diagnosis of systemic lupus erythematosus (SLE) choroidopathy and guided its further management with systemic immunosuppression, hemodialysis and plasmapheresis. There was a rapid resolution of the retinal and choroidal findings with visual recovery over the next month. Systemic lupus erythematosus (SLE) is a common autoimmune disease characterized by the development of autoantibodies to nucleic acid-containing cells. Systemic findings include lupus nephritis, dermatological, musculoskeletal or hematological manifestations . CommonlA 55-year-old female presented to her local physician with a recent two-month history of bilateral lower limb swelling which had increased since the last three days, facial swelling and red facial rash along with a decreased frequency of micturition. Her previous significant medical history included systemic hypertension and hypothyroidism currently being treated. Baseline investigations revealed a fasting blood glucose of 73.8 mg/dl , an elevated serum creatinine of 2.56 mg/dl  and a blood urea nitrogen of 59.71 mg/dl . An abdominal ultrasound showed slightly altered renal cortical echotexture suggestive of medical renal disease. Mild fullness of the bilateral pelvicalyceal system and entire ureter was noted along with mild urothelial thickening noted along the entire pelvicalyceal system and ureters. Following a urological consult, she underwent a cystoscopy with urethrotomy with bilateral retrograde ureteropyelography (RUP) for suspected hydronephrosis.A nephrologist’s opinion was sought, and subsequent investigations revealed a positive antinuclear antibodies (ANA) +++ test  and positive anti-double-stranded DNA (dsDNA) testing , and glomerular basement membrane (GBM) antibody testing was negative with equivocal test results for perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) (myeloperoxidase (MPO))  and negative results for cytoplasmic ANCA (c-ANCA) antibodies . A needle biopsy of the kidney revealed focal necrotizing, diffuse proliferative and crescentic glomerulonephritis with diffusely thickened capillary walls featuring predominantly cellular crescents over 3/36 of sampled glomeruli and tuft necrosis in 4/36 glomeruli. Direct immunofluorescence (DIF) studies revealed glomerular capillary and mesangial immune complex deposits (immune-mediated crescentic and diffuse proliferative glomerulonephritis). Patchy acute tubular injury is noted. A clinical diagnosis of type IV lupus nephritis with activity and chronicity was made.At this time, an ophthalmic opinion was sought for her 15-day history of bilateral gross visual loss. Records reveal a visual acuity of 6/18 bilaterally with a diagnosis of bilateral multiple exudative retinal detachments. An optical coherence tomography (OCT) scan at the time reported retinal pigment epithelium (RPE) and serous retinal detachments bilaterally. Based on a confirmed diagnosis of systemic lupus erythematosus with lupus nephritis, she was treated with systemic steroids (prednisolone 60 mg/day) and intravenous cyclophosphamide . Hemodialysis was initiated for persistent anuria and a raised serum creatinine of 6.4 mg/dl . She was administered three doses of methylprednisolone 500 mg intravenously, and she was transferred to our center.3; normal: 4,000-11,000/mm3) with a predominant neutrophilic response . Her serum creatinine was 4.35 mg/dl . As she was mildly febrile, blood and urine cultures were sought, which grew Escherichia coli. The presence of a bloodstream infection precluded the use of further immunosuppression in the form of rituximab or calcineurin inhibitors.On examination, she was pale with gross anasarca and bilateral pitting edema of the lower limbs. Vital parameters including her blood pressure (140/70 mmHg), heart rate (92/min) and oxygen saturation (98%) were normal. Examination of her respiratory and cardiovascular systems was normal. She was comprehensively investigated with routine hematological tests, renal and liver function tests. Relevant findings included mild anemia  and leukocytosis  revealed her near vision to be N36 without any further improvement. A slit-lamp examination of either eye was normal as were her intraocular pressures and pupillary reactions. No evidence of anterior uveitis (cells/flare) or vitreous cells was detected. A dilated fundus examination revealed multiple yellowish lesions throughout the posterior pole consistent with pockets of subretinal fluid in the right eye Figure . A sweptVascular access was re-established via a right-sided internal jugular tunnel cuffed catheter (TCC), and a decision was made to employ plasmapheresis (PLEX) along with her routine thrice-weekly hemodialysis. Additionally, the systemic steroids were continued with the addition of hydroxychloroquine (200 mg/day) and cilnidipine (10 mg/day). She was monitored with visual acuity assessment, slit-lamp examination, dilated fundus examination and OCT scans weekly. At her third follow-up (day 22) following five sessions of plasmapheresis and continued immunosuppressive treatment, her vision had improved to 6/9 unaided bilaterally and to N6 with the appropriate correction. There was a near-complete regression of the exudative retinal detachments bilaterally with pigmentary changes Figures , 2C. TheSystemic lupus erythematosus (SLE) is a multisystem autoimmune disease with protean manifestations. Several phenotypes exist, and patients may present with numerous clinical manifestations ranging from a mild dermatological involvement to severe multiorgan disease. The pathogenesis is complex and is currently thought to be due to the activation of autoimmunity in genetically susceptible patients. The underlying pathogenetic mechanism is an activation of T and B cells which then leads to cytokine release, complement activation and autoantibody production . Lupus aSystemic manifestations include dermatological , musculoskeletal (arthritis), hematological (cytopenia), cardiovascular , central nervous system  and renal (lupus nephritis). SLE can affect virtually every tissue of the eye. Commonly described findings include as follows: A) Orbital manifestations: This includes a vasculitis that manifests as proptosis, painful orbital areas, defective vision and restriction of extraocular movements. Nonperfusion of the globe and extraocular muscles is common and may lead to optic nerve ischemia. Myositis may present similarly and is best diagnosed on computed tomography or ultrasound as an enlargement of one or several extraocular muscles. B) Ocular surface manifestations: The commonest ocular manifestation of SLE is keratoconjunctivitis sicca which occurs in the majority and is usually due to an aqueous layer deficiency. C) Scleral/corneal manifestations: These include a mild episcleritis or a phenotype of scleritis which typically presents with higher degrees of pain and may potentially be sight-threatening. Phenotypes of scleritis reported include anterior and posterior scleritis. D) Retinal manifestations: These may be seen in up to 29% of patients with active disease. Retinal microangiopathy consisting of small intraretinal hemorrhages and cotton wool spots is the commonest manifestation. Mechanisms of causation include immune complex deposition in the vessel wall with subsequent inflammation. A subset of patients present with retinal vasculitis with retinal venular or arteriolar inflammation. This is closely linked to the presence of antiphospholipid antibodies including anticardiolipin. Several reports have highlighted central retinal artery/vein occlusions or retinal ischemia as important causes of visual morbidity. E) Optic nerve lesions in the form of optic neuritis or ischemic optic neuropathy have been reported [Lupus choroidopathy is a rare ocular manifestation with approximately 40 patients described till date in the literature . In a reNguyen and co-workers described the management of three cases of SLE choroidopathy and included a literature review which included 25 previously published papers . These iJabs et al. described their experiences with six patients who presented with serous detachments of the retinal pigment epithelium and retina in a multifocal pattern that had its fluorescein angiographic correlates in several areas of late hyperfluorescence within the sensory retinal detachments . Good syThese reviews were described prior to the widespread adoption of OCT in retinal practices. Kouprianoff et al. described the systemic, clinical and OCT findings of a 16-year-old female with SLE . OCT revThe patient we describe is a 55-year-old woman with a previous diagnosis of SLE, who developed lupus nephritis and bilateral severe gross visual loss. She was treated with immunosuppressives, hemodialysis and plasmapheresis (PLEX). PLEX probably works in several ways: it may remove autoantibodies and circulating immune complexes or may replace abnormal proteins. PLEX has so far been used to treat patients with severe neurological manifestations of SLE including psychosis or acute myelopathy. Available literature for the use of PLEX in the ocular manifestations of SLE is limited. Papadaki and co-workers have described the successful treatment of two patients with retinal vasculitis who were treated with PLEX and immunosuppression .www.pubmed.gov) using the search terms “bacillary layer detachment” and “systemic lupus erythematosus” returned no results and suggests that our findings constitute a novel finding and that the spectrum of bacillary layer detachment is expanded to include SLE choroidopathy.Clinical findings included RPE detachments, sub- and intraretinal fluid and bacillary detachments. A widespread choroidal vasculitis with consequent leakage into the subretinal and intraretinal space appears to account for our observed findings. Bacillary detachments are a novel OCT sign recently described that may denote a split between the myoid and ellipsoid layers of the inner photoreceptor segment usually following outer retinal lesions or infections/inflammations of the choroid. It has been reported in numerous conditions including toxoplasmic retinochoroiditis, Vogt-Koyanagi-Harada disease and chronic serous chorioretinopathy . In our The patient we describe had classic clinical and investigational findings of SLE. The development of lupus nephritis with the consequent choroidal lesions led to a profound visual loss. Fundus examination and OCT studies established the diagnosis of SLE choroidopathy and guided its further management with systemic immunosuppression, hemodialysis and plasmapheresis. There was a rapid resolution of the retinal and choroidal findings with visual recovery over the next month.SLE choroidopathy is an infrequently reported complication of SLE. Limited cases have been reported in the literature with the vast majority presenting with multifocal exudative retinal detachments with findings of intraretinal and subretinal fluid collections. Appropriate treatment usually results in good anatomical and visual recovery. The relatively new modality of OCT permitted us a good characterization of the retinal/choroidal disease and allowed us to describe a novel finding of bacillary layer detachment in this patient. Serial follow-up allowed us to monitor the resolution of the disease.


High-quality social contacts are important for older adult’s emotional well-being whereas narcissism, characterized by self-centeredness, may undermine the quality of personal relationships. Narcissism may be associated with poorer quality relationships because narcissistic adults are more self-centered in their daily social interactions. The current study examined the associations between linguistic features of conversation throughout the day and narcissism using a machine learning approach. Older adults aged 65–89  wore an unobtrusive electronically activated recorder (EAR) throughout the day for 4 to 6 days. The EAR was activated 30 seconds every 7 minutes to capture conversations occurring in a natural setting. The sound files that contained participant’s speech  were transcribed verbatim. We used Linguistic Inquiry and Word Count (LIWC) to extract linguistic features from the transcriptions . Linguistic features were analyzed using random forest algorithm which is a supervised machine learning method that can evaluate features’ performances in predicting older adult’s narcissism. The model reached an accuracy of 62% and results showed that total word count, more auxiliary verbs , more swear words , and less assent  were the most powerful predictors of narcissism. Drawing on sound files collected from real-life interactions, findings indicate higher usage of aggressive and disagreeable words among more narcissistic individuals, which probably leads to poorer quality relationships with social partners. Interventions aiming to improve contact quality and emotional well-being may consider individuals’ word use in daily interactions.


Antiphospholipid syndrome (APS) is a rare autoimmune multisystem disease characterised by thrombosis and pregnancy morbidity in the presence of persistently elevated titres of: lupus anticoagulant, anticardiolipin and/or anti-glycoprotein 1. It may be primary  or secondary ). Recent publications highlighted clinical criteria limitations for children and raised awareness of the burden and prevalence of non-criteria manifestations in this population. This case report adds further weight to the need to raise multi-specialty awareness of non-criteria manifestations to aid recognition and treatment of this rare condition with potentially severe sequelae.13-year-old female with SLE diagnosed aged 8 in India with bilateral optic neuritis occurring two months later. ANA positive at diagnosis with low complement and thrombocytopenia. Treated with prednisolone and hydroxychloroquine. Patient moved to the UK aged 9; initial abnormal bloods: mildly positive ANA (ENA negative), thrombocytopenia, strong lupus anticoagulant. As serology not strongly suggestive and optic neuritis rare in lupus diagnosis questioned. Ophthalmology review confirmed bilateral optic atrophy without evidence of previous vasculitis. There was debate whether the post-retinal demyelination was due to antiphospholipid syndrome or a primary demyelinating condition. Hydroxychloroquine stopped and azathioprine started. Following normal neurology investigations  concluded if patient developed new APS-related symptoms or worsening visual evoked potentials anticoagulation would be discussed. Patient remained stable over four years with chronic thrombocytopenia and ESR persistently elevated. Azathioprine changed to Mycophenolate mofetil (MMF) due to side effects.Routine medication monitoring bloods in 2022 showed ESR 97, CRP 78, Platelets 61. Review identified vasculitic rash on soles of both feet with palpable nodules and normal pulses. Further investigation confirmed antiphospholipid antibody triple positivity. Aspirin commenced, hydroxychloroquine restarted, MMF dose increased and rituximab administered. Left foot rash settled but right progressed with toe discolouration and numbness. Skin biopsy considered but not performed due to skin integrity concerns. Foot pulses remained present and normal. Bilateral lower limb doppler reported as normal; increased symptoms resulted in CT angiogram which revealed bilateral non-occlusive popliteal thrombus and left pulmonary embolus. Subsequent echocardiogram was normal. Patient was anticoagulated with low molecular weight heparin followed by warfarin. Vascular surgical team advocated medical management and patient received seven infusions of Iloprost followed by Sildenafil. She achieved near total resolution of skin changes to toes with only minimal loss of skin over tip of right great toe. Patient will now require long-term anticoagulation.APS was considered in initial differential diagnosis but patient did not meet current clinical criteria as no past evidence of thrombosis. Lupus anticoagulant was consistently strongly positive and anticardiolipin repeatedly negative. As anti-B2 glycoprotein 1 antibody is not routinely tested and must be verbally requested, it was only checked once (negative) prior to discovery of triple positivity.ANA reported as strongly positive at time of SLE diagnosis but reviewing original notes from India titre was 1:100 and therefore not highly convincing. ENA negative and complement and white cell count normal on repeat testing since. Therefore, it is probable that this patient has primary APS as opposed to secondary APS in association with SLE. However, it is possible that this patient may develop more symptoms of SLE over time.When this patient presented with foot rash there were high numbers of children presenting with varying severity of painful, itchy toes coined ‘covid toes’ due to suspected link to SARS-CoV-2 infection. Patient had exposure history, and COVID antibody serology was difficult to interpret due to recent vaccination. Dermatology found appearance to be consistent with ‘covid toes’ and advised supportive treatment. The triple APS antibody positivity result provided probable aetiology. Providing evidence of thrombus was problematic with false reassurance from apparently normal lower limb arterial doppler when actually popliteal arteries were not checked in view of the presence of normal flow proximally at the groin and distally in the feet.This case highlights the need to continue to search for thrombus in presence of high titres antiphospholipid antibodies and particularly in the case of triple positivity as although patient presented with colour change to toes, she was entirely asymptomatic from her PE and her left foot improved spontaneously despite a left popliteal thrombus also being present.Non-criteria manifestation of thrombocytopenia (occurs in 25% paediatric APS patients) was present throughout and patient had past history of haematuria . A paediatric specific APS criteria including these may have resulted in earlier detection of triple antiphospholipid antibody positivity and thus earlier treatment escalation and possible avoidance of thrombus.It has been reported that a high proportion of children with positive antiphospholipid antibodies don’t develop a thrombus. However, it is interesting that our patient was entirely asymptomatic from her pulmonary embolus which was an incidental finding on her CT angiogram. This prompts a discussion about how much imaging should be performed in those with high levels of persistent positive antiphospholipid antibodies.Rituximab resulted in normalisation of platelet count and ESR for the first time since initial presentation. Anticardiolipin antibodies normalised, lupus anticoagulant decreased from strong to moderate and anti-B2 glycoprotein levels decreased but remained positive. Rituximab is a recognised treatment for catastrophic antiphospholipid syndrome (CAPS) but not routinely used in APS. The consistently raised ESR in an apparently clinically well patient is a reminder to continue to search for causes of inflammation. As the CRP was largely in normal range, this demonstrates the unique value of the ESR.In view of anti-B2 glycoprotein 1 antibody requiring to be verbally requested, discussions are ongoing with the laboratory department regarding the possibility of electronic request and a comment with recommendation to check other two antiphospholipid antibodies following one positive antibody result.As a result of this case, a plan will be put in place to ensure annual screening of antiphospholipid antibodies in all juvenile SLE patients in our care.It is hoped that this case report promotes discussion amongst the paediatric rheumatology community regarding further research required for development of paediatric specific APS criteria and management.


Older adults with cognitive disability are worse off with being up-to-date with preventive care and routine dental care is not considered a clinical preventive visit covered by insurance for this population. I examine disparities in access to dental and clinical preventive services  in the past year in 28,068 older adults with cognitive disability using the nationally representative Medical Expenditure Panel Survey from 2009-2016. I conduct multivariate logistic regressions and find older adults with cognitive disability vs. no disability have higher odds of receiving annual blood pressure check  but lower odds for having an annual dentist visit  with only one-tenth of those with cognitive disability report having dental insurance. These findings have implications for integrated community-and-clinical care partnerships for closing the gap for routine dental care services among older adults with cognitive disability.


Student training was suspended in most post-acute settings in the United States due to the COVID-19 pandemic. Through a collaborative partnership between a university and a healthcare organization we offered a virtual telehealth clinical experience to prepare student physical therapists for practice in a skilled nursing facility (SNF) setting. 35 students engaged virtually for 80 hours with two clinical instructors. The curriculum included eight virtual learning modules along with four telehealth patient encounters that exposed students to interdisciplinary teams in the SNF context. Students completed a retrospective pre/post Self-Perception of Learning Survey. Results demonstrated students’ self-perception of learning was significantly increased implying an improved ability to practice in the SNF setting. This approach advanced student learning in patient care management, interprofessional practice, and telehealth practice in the SNF setting. Future work is planned to expand the program to include 20 physical therapy, occupational therapy, and speech and language pathology students.


Communications Biology 10.1038/s42003-021-02966-6, published online 11 January 2022.Correction to: The original version of this Article was missing data accessions (SRR19134783 and SRR19134809) in the Data Availability statement.“All genome sequence data are available at the GenBank under the Accession number JABETM000000000. Raw sequence data are available at the NCBI SRA site with the accession numbers SRR15444039 and SRR15254972.”This error has been corrected in the HTML and PDF versions of the Article, as follows:“All genome sequence data are available at the GenBank under the Accession number JABETM000000000. Raw sequence data are available at the NCBI SRA site with the accession numbers SRR15444039, SRR15254972, SRR19134783 and SRR19134809.”


Life-threatening bleeding after oocyte retrieval is unusual. We report a case of massive vaginal bleeding requiring transcatheter arterial embolization (TAE) after transvaginal US-directed follicle aspiration for oocyte retrieval and provide a brief review of cases in which the pseudoaneurysm of the injured artery was managed with a TAE approach. A 40-year-old woman presented massive vaginal bleeding after transvaginal ultrasonography-directed follicle aspiration for oocyte retrieval. Contrast-enhanced computed tomography revealed active bleeding from the uterine ostium. Transcatheter arterial embolization was performed for a pseudoaneurysm of the right pudendal artery to manage the hemorrhage. Potentially life-threatening bleeding should be recognized as a rare complication after oocyte retrieval to promptly establish the diagnosis and preserve the uterus. In vitro fertilization (IVF) is a common treatment worldwide for people who cannot conceive naturally. IVF is generally very safe, and those undergoing IVF rarely experience any health or pregnancy-related problems associated with the procedure . TransvaHere, we report a case of massive vaginal bleeding requiring transcatheter arterial embolization (TAE) after transvaginal US-directed follicle aspiration for oocyte retrieval and review the relevant literature. A 40-year-old woman with a history of primary infertility for three years was transferred using emergency transportation from another hospital. She presented massive vaginal bleeding. Her vital signs were as follows: heart rate, 135 bpm; blood pressure, 80/65 mmHg; and respiratory rate, 25 breaths/min. The hemoglobin level was 6.1 g/dL. The patient became hemodynamically unstable and had hypotension. She had undergone transvaginal US-directed follicle aspiration to retrieve oocytes 6 h earlier at another hospital. This was her second attempt at oocyte retrieval.The patient had no history of surgical intervention. Her left ovary with a chocolate cyst due to a history of endometriosis adhered to the uterus and was unsuitable for oocyte retrieval. Further, the right ovary was firmly fixed behind the middle uterine segment. Her physician assessed the difficulty in obtaining oocytes with conventional follicle aspiration through the vaginal fornix from the right ovary because the right ovary was malpositioned. In addition to conventional follicular aspiration through the vaginal fornix, transmyometrial oocyte retrieval was performed for the right ovary under US guidance using a 19-gauge aspiration needle. To perform transmyometrial puncture, an aspiration needle was inserted obliquely through the lower uterine segment to reach the right ovary. Color Doppler was used to check blood flow around the follicles and myometrium. Three oocytes were retrieved. 10 min after the procedure, Pulsatile vaginal bleeding and pain persisted after the procedure. Gauze packing did not stop the vaginal bleeding. She was transferred to our hospital using emergency transportation because she became hemodynamically unstable and developed hypotension with gauze packing alone.Contrast-enhanced computed tomography (CT) on admission revealed active bleeding from the uterine ostium suggesting a ruptured pseudoaneurysm . TAE wasIVF is an established treatment modality for infertility worldwide. In assisted reproduction, US-guided retrieval of oocytes through the vaginal fornix is now accepted as a safe and well-tolerated method involving a low overall complication rate . AlthougIn our case, transmyometrial oocyte retrieval was performed in addition to conventional follicular aspiration through the vaginal fornix. This might have increased the risk of hemorrhage because vascular penetration with aspiration can cause myometrial trauma .Very rare cases require TAE to stop bleeding associated with oocyte retrieval. We searched PubMed and Google Scholar to review the available literature (published until April 2022) on massive vaginal bleeding requiring TAE after transvaginal US-directed follicle aspiration for oocyte retrieval using the key terms “oocyte retrieval,’’ and “arterial embolization’’. There were six cases (including our case) requiring TAE after transvaginal US-directed follicle aspiration for oocyte retrieval due to pseudoaneurysm . MoreoveThe management of pseudoaneurysms based on the fertility of the case may be controversial . TAE hasIn conclusion, it is important to recognize pseudoaneurysm as a rare complication after IVF to achieve a prompt diagnosis and enact uterus-preserving management for this potentially life-threatening disorder. Both the fertility specialist and general obstetrician/gynecologist should be aware of this to ensure better counseling of their patients and effective treatment.


Limits to in-person social interaction increased the risk of loneliness during the Covid-19 pandemic. This study examines how gender and previous information communication technologies (ICT) experience could stratify how ICT-mediated social interactions related to loneliness during the COVID-19 pandemic. We employed National Health & Aging Trends Study data collected in 2018 and 2020-2021  to examine how the email and video call use before and during the COVID-19 pandemic was associated with loneliness and how the degree of impact differed by gender and previous ICT experience. In total, 35% reported feeling lonely some days or more frequently during the COVID-19 pandemic. Preliminary analysis showed older adults using video calls during the COVID-19 pandemic were 1.24 times more likely to report loneliness. This association was stronger among men than women and those who did not use ICT preceding the pandemic than those who used.


Fragmented communication between care partners, health care providers, and adult day centers around the needs of persons living with dementia (PLWD) contributes to avoidable health care utilization. CareMOBI, is a user-centered mobile application that streamlines information exchange around datapoints relevant to the care of PLWD. CareMOBI facilitates team-based communication around emerging clinical problems by uniquely integrating the knowledge and day-to-day observations of adult day center staff and care partners. We present a stakeholder engaged approach to iteratively designing and validating an initial prototype. Through interviews and focus groups with adult day center staff (n=31), primary care providers (n=22), and family caregivers (n=13) we identified barriers to communication across settings. We then visually mapped the domains of a future app which we subsequently validated and refined with end-users (n=25). We present our current prototype which synthesizes these findings and addresses key barriers to information exchange across community settings serving PLWD.


A 74-year-old man with a history of retrosternal oesophageal reconstruction was referred for surgical treatment of mitral valve regurgitation and coronary artery disease. He underwent mitral valve replacement combined with coronary artery bypass grafting through a left thoracotomy. Combined mitral valve replacement and coronary artery bypass grafting through a left thoracotomy were feasible in this patient with a retrosternal neo-oesophageal conduit. Cardiac surgery in patients with a history of retrosternal oesophageal reconstruction remains challenging. Cardiac surgery in patients with a history of retrosternal oesophageal reconstruction remains challenging. We report a successful mitral valve replacement (MVR) combined with coronary artery bypass grafting (CABG) through a left thoracotomy in a patient with a retrosternal neo-oesophageal conduit.A 74-year-old man was referred for surgical treatment of mitral valve regurgitation and coronary artery disease. He underwent oesophageal surgery for oesophageal carcinoma with retrosternal gastric tube reconstruction through a right thoracotomy 11 years ago. Transthoracic echocardiography showed severe mitral valve regurgitation due to a flail mitral valve posterior leaflet and mildly reduced left ventricular systolic function with an ejection fraction of 43%. Coronary angiography revealed occlusion of the left anterior descending artery. Computed tomography revealed that the neo-oesophageal conduit was located just beneath the upper and lower parts of the sternum Fig. a. The oret al. reported 8 cardiac surgical cases after extra-anatomic oesophageal reconstruction   . They peet al. reported a case series of 16 patients who underwent the left thoracotomy approach for multiple redo mitral valve operations (Mitral valve surgery through a left thoracotomy is rarely performed in selected patients. Suzuki erations . All proIn this case, mitral valve repair was not performed mainly because the intraoperative transoesophageal echocardiography could not be used. In addition, when complex mitral valve repair was needed, the time required for CPB and aortic cross-clamping might have been extended because of our inexperience with this approach. Ultimately, we could perform MVR and CABG through a left thoracotomy without any difficulty. Combined MVR and CABG through a left thoracotomy was feasible in a patient with a retrosternal neo-oesophageal conduit.


Bipolar disorder is one of the most frequent psychiatric disorders among suicidal patients. A large part of patients with bipolar disorder (30–50%) will attempt suicide. Suicidal ideation being a major risk factor of suicidal act, it is crucial to better characterize patients with suicidal bipolar depression . The aim of this study was to characterize suicidal bipolar depressed patients in comparison with non-suicidal depressed patients in terms of clinical characteristics, evolution of depression and suicidal ideation course over time, and risk of suicide attempt during follow-up.Among patients with bipolar disorder recruited from the network of FondaMental expert centres for bipolar disorder between 2009 and 2017, we selected patients with at least mild depression and without current manic symptomatology at baseline (N = 938). Suicidal depression was defined by a baseline score ⩾2 for item 12 of the QIDS-SR (28.9%). A subsample of about 300 patients  was followed up for 2 years.Baseline clinical features  were more severe in patients with without suicidal depression. Suicidal patients tended to remain more suicidal throughout the followup .Depressed bipolar disorder patients reporting suicidal ideation had more severe clinical features and were more prone to report persistent suicidal ideation during the follow-up, independently of thymic state. Clinicians should closely monitor this subgroup of patientsNo significant relationships.


We describe a case of epipericardial fat necrosis.Epipericardial fat necrosis is an inflammatory condition in which the pericardial fat pad necrotizes resulting in surrounding inflammation. This condition mimics more ominous pathology in clinical presentation and radiographic findings. Management is supportive with oral analgesics. A 39-year-old male presented to the emergency department (ED) for three days of right-sided, pleuritic chest pain. The patient denied any preceding trauma or illness. Examination revealed no overlying skin changes or reproducible chest wall tenderness, although lung sounds were noted to be diminished near the right lung base. His vital signs were as follows: temperature of 98.2° Fahrenheit; respiratory rate of 17 breaths per minute; pulse oximetry of 95% on room air; blood pressure of 135/82 millimeters of mercury; and heart rate of 92 beats per minute.Chest radiograph revealed a right pleural effusion with right base consolidation suspicious for pneumonia . Based oEpipericardial fat necrosis is a rare benign condition5CPC-EM CapsuleWhat do we already know about this clinical entity?Epipercardial fat necrosis is a self-limited, inflammatory condition which often causes chest pain and radiographic findings suggestive of more ominous pathologies.What is the major impact of the image(s)?These images demonstrate the characteristic fat pad changes in combination with radiographic findings that may also be present with more ominous pathologies.How might this improve emergency medicine practice?Early recognition of this etiology may reduce excessive imaging and aid in the initiation of appropriate management.


The low prevalence of some genetic neuro-developmental syndromes associated to psychiatric disorders requests to be integrated in human genome-phenome databases from which pleiotropy can be compiled from by systematic integration of phenotypes associated with genetic loci using phenomic inference tools. Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder related to elastin gene at 7q11.23. Anxiety, depression and attention problems are the main behavioral problems found in WBS with no gender differences. Significant differences between cohorts are reported in particular regarding somatic complaints and aggressive behavior.Here, we report a Tunisian cohort of WBS patients for whom clinical behavioral phenotypes as well as genetic features are detailed.Sixteen patients from Sfax, Tunisia were referred for genetic assessment due to a suspected WBS syndrome.Genetic evaluation using fluorescent in situ hybridization confirmed 7q11.23 microdeletion in only eight patients. Comparison of detailed behavioral phenotypes revealed differences between age groups, gender groups and genetic groups. Anxiety and depression were recorded in the two older male patients and aggressive behavior was recorded in only two boys. The severity of behavioral features were dependent to familial environment and to parental socio-economic and educational levels.A more complete understanding of phenomic space is critical for elucidating genome-phenome relationships mediating neurodevelopmental disorder associated to psychiatric diseases for assessing and managing psychiatric and behavioral risks in young syndromic children.No significant relationships.


MUC2 mucin, produced by colonic goblet cells, forms a mucus bilayer that provides a physical barrier between potential pathogens in the lumen and the underlying epithelial cells. Mucus is thus the first line of innate host defense in the gastrointestinal (GI) tract. Many GI diseases including inflammatory bowel disease and colon cancer affect the glycosylation of mucus. Goblet cells produce a variety of proteins that are associated with the mucus layer. Of these proteins, FCGBP is of significant interest due to its structural similarities to MUC2 mucin with unknown functions. In this study, we investigated how a missense mutation in FCGBP altered the glycosylation of goblet cell MUC2 and affected its barrier functions.Hypothesis: A missense mutation in FCGBP results an impaired mucus layer by the altering glycomic profiles of goblet cell mucins. Specific aims:1) To determine mechanistically how FCGBP impeded the structural integrity of the mucus layer2) To quantify MUC2 glycoprotein modifications in the altered mucus layerTo investigate whether FCGBP impaired mucus barrier functions, two cell types were investigated: wildtype LS174T (WT) MUC2 mucus-producing goblet cells and LS174T cells with a missense mutation in FCGBP (FCGBP MS). To determine if FCGBP MS led to loss in barrier function in the mucus layer, the penetration of 0.2, 1, and 2 μm fluorescent beads (to mimic bacteria) through the mucus layer were quantified. To determine if the differences in penetrability were caused by differences in MUC2 glycosylation in the goblet cell lines, sensitive glycomic analyses were performed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and capillary electrophoresis with laser-induced fluorescence detection (CE-LIF). Both intact cells and isolated MUC2 mucin granules were analyzed. To determine if differences in the glycomic profiles was caused by differences in glycotransferases, RT-PCR was performed on over 30 human glycosyltransferases.FCGBP MS cells exhibited significant loss in MUC2 mucus barrier function as quantified by fluorescent beads penetration through the mucus layer in a temporal manner. FCGBP MS cells exhibited an altered glycomic profile with a notable increase in sialylated glycans as quantified by HPLC-MS. The increase in sialylated glycans was associated with a significant increase in sialyl-transferase expression in FCGBP MS cells.These data demonstrate that a single missense mutation in FCGBP altered the penetrability of the mucus layer associated with an increase in sialylated proteins, a signature hallmark of numerous colonic diseases. FCGBP was critical in providing structural integrity of the mucus layer and maintenance of goblet cell glycosylation profiles.CIHRNone Declared


Aging is a complex biological process associated with progressive loss of physiological function and susceptibility to several diseases, such as cancer and neurodegeneration. As senescence burden increases with aging and becomes a risk factor for many age-related diseases we are specifically interested in senescence-derived aging signatures. We use cutting-edge proteomic workflows to investigate both the senescence-associated secretory phenotype (SASP) in tissue cultures. We are subsequently examining exosome proteins as well as lipid cargo in plasma from human young (20–26 yrs) and old cohorts and old (60–66 yrs) individuals. We will also present current work assessing senescence markers in cartilage and bone targeting underlying mechanisms and options for intervention for osteoarthritis. Overall, our focus is specifically directed towards senescence-derived biomarkers of aging.


Stenosis is a common complication of haemodialysis arteriovenous accesses. Endovascular approaches with percutaneous transluminal fistuloplasty have largely replaced open surgical approaches as first line treatment. Vessel rupture is an uncommon complication of fistuloplasty and most reports describe venous rupture. Stent-graft deployment can salvage this, however, its use requires careful assessment of the distal vasculature. Arterial rupture with fistuloplasty has rarely been described in the literature. This is a novel case describing the use of a BeGraft coronary stent-graft to manage juxta-anastomotic arterial rupture and pseudoaneurysm complicating fistuloplasty.A 77 year old female with end stage renal failure secondary to systemic amyloid light chain type amyloidosis was referred for a suspected radio-cephalic arteriovenous fistula stenosis after difficulty cannulating with poor flow during dialysis and clinical reduction in the fistula thrill. Both Doppler ultrasound and intravenous fistulography confirmed a venous stenosis 2 cm distal to the anastomosis. The stenosis was treated by fistuloplasty, however, this was complicated by a rupture of the juxta-anastomotic arterial segment intraoperatively. Intermittent balloon tamponade was used to minimise extravasation although a pseudoaneurysm formed within the damaged arterial segment. The patient’s distal neurovascular status was assessed using the Barbeau test and we sonographically confirmed adequate retrograde arterial flow via a complete palmar arch directing blood from the ulnar artery. After discussion with the renal transplant team, a 4 mm BeGraft coronary stent-graft was deployed to control haemorrhage and bypass the pseudoaneurysm until adequate haemostasis and fistula flow was achieved. Follow-up 3 months post-procedure reported the patient continued with haemodialysis using the stented fistula with no further complications.To our knowledge, this is the first case report describing the application of BeGraft coronary stent-grafts to salvage fistuloplasty of a radio-cephalic arteriovenous fistula stenosis complicated by juxta-anastomotic arterial rupture and pseudoaneurysm formation. We demonstrate the safety and short-term efficacy of this technology. Fistuloplasty, or percutaneous transluminal angioplasty (PTA), remains the first-line treatment of arteriovenous fistula (AVF) stenosis with a technical success rate of 90%  type amyloidosis on long term haemodialysis was referred to the interventional radiology department following difficulty in cannulating her AVF and clinical reduction in the palpable fistula thrill. Her significant medical comorbidities include type 2 diabetes mellitus, hypertension, hypercholesterolaemia and a pacemaker for Mobitz type 2 second degree atrioventricular block.Doppler ultrasound revealed a stenosis 2 cm distal to the anastomosis. With systemic heparinisation, we performed fistulography under intravenous sedation  and local anaesthetic (10 ml 1% Lidocaine). Glyceryl trinitrate (800 μg) and Amlodipine (10 mg) were administered during the procedure due to a systolic blood pressure of over 200 mmHg on a background of known hypertension. This controlled the systolic pressure to 150 mmHg.Under ultrasound guidance, retrograde puncture of the fistula was performed. A 5F sheath was inserted and the catheter and wire were successfully passed across the stenotic lesion. The initial venogram confirmed a single juxta-anastomotic venous segment stenosis Fig. .Fig. 1AnThis was initially dilated with a 4 mm Sterling balloon (Boston Scientific) which resulted in suboptimal reduction of the stenosis after which a 5 mm Sterling balloon was used to overcome the tight stenosis. To achieve optimal dilatation of the affected vessel, a short segment of the balloon was positioned and inflated within the arterial segment to attain adequate vessel patency and to prevent migration of the balloon proximally due to arterial-flow back pressure. This was complicated by rupture at the juxta-anastomotic radial artery segment which immediately presented as pain and swelling in the patient’s forearm and was confirmed by fistulography Fig. .Fig. 2ShIntermittent balloon tamponade was maintained with a 3 mm balloon at the level of contrast extravasation. To ensure safety of the distal limb whilst the balloon was inflated, the neurovascular status of the patient was clinically assessed together with ultrasound of the radial artery distal to the fistula which demonstrated adequate retrograde blood flow from the complete palmar arch via the ulnar artery. This was further confirmed with a Barbeau test which showed no dampening of the pulse oximeter waveform on the ipsilateral thumb with balloon inflation. Confirmation of the above allowed for prolonged balloon tamponade for a total duration of 30 minutes without concern for neurovascular compromise to the distal limb.Whilst intermittent balloon tamponade minimised extravasation, a small pseudoaneurysm subsequently formed within the short arterial segment Fig. . After dThe completion fistulogram demonstrated excellent flow through the fistula with no evidence of active bleeding and complete exclusion of the pseudoaneurysm Fig. . There wThe patient recovered well post-procedure and was admitted overnight for monitoring and neurovascular observations. Her post-operative haemoglobin levels were within normal limits . The forearm swelling improved significantly, and no neurovascular complications were noted the following morning. The patient was reviewed in haemodialysis clinic 3 months later and successfully continued with haemodialysis through the stented fistula, reporting no further complications.PTA induced arterial rupture is a rare but serious complication in percutaneous coronary intervention and has also been reported for femoral, popliteal, iliac and renal artery interventions  covered Cobalt-Chromium stent-graft, to manage juxta-anastomotic arterial rupture and pseudoaneurysm complicating fistuloplasty for a radio-cephalic AVF stenosis.Whilst BeGraft is commonly used in coronary intervention, a small number of studies have reported application of a BeGraft coronary stent-graft within a comparable non-coronary context such as in traumatic or iatrogenic injury to the anterior tibial artery and other small vessels including the renal, gluteal and ascending cervical arteries  or Fluency Plus (Bard), both self-expanding ePTFE covered Nitinol stent-grafts, would not have met these requirements due to their larger profiles. Furthermore, balloon-expandable stent-grafts allow for more precise positioning as they do not require stepwise deployment, making the BeGraft coronary stent-graft the most suitable option for this application.Sufficient segments of proximal and distal landing zones were identified for stent-graft placement to adequately exclude the pseudoaneurysm without crossing the anastomosis. Had an adequate distal arterial landing zone not been present, it would have been feasible to cross the anastomosis with the stent-graft as we had demonstrated adequate retrograde flow from the ulnar artery via the intact palmar arch. This alternative placement would have been suboptimal as the angulation of the anastomosis would have increased the risk of stent fatigue. Both explant and in silico data demonstrate that pulsatile fatigue-related damage of stent-grafts concentrate in areas of severe angulation and bending (Dalbosco et al. Irrespective of the approach used to treat AVF arterial rupture and pseudoaneurysm, whether balloon tamponade or stent-graft deployment is used or the positioning of the stent-graft, it is vital to assess for adequate retrograde blood flow via the palmar arch from the ulnar artery. This can be clinically proven by neurovascular assessment, the Barbeau test and sonographically by ultrasound of the distal vasculature. If necessary, prolonged tamponade in arterial rupture and stent-grafting across the anastomosis can be safe with confirmation of the above.Despite the high technical success rate demonstrated by stent-grafts in both AVF vessel rupture and pseudoaneurysms, there are a few limitations. Covered stent-grafts are not designed for repeat cannulation which means once deployed, the area must be marked to avoid cannulation over that site as in our patient.In conclusion, juxta-anastomotic arterial segment rupture is a rare complication of fistuloplasty that can be managed with endovascular stent-graft deployment. Clinical assessment of the neurovascular status and adequate retrograde palmar arch flow via the ulnar artery are key to ensuring safe balloon tamponade and stent-graft deployment. We demonstrate that the BeGraft coronary stent-graft is safe and effective in the short-term. Its long-term success in salvaging failed or complicated fistuloplasty of AV accesses requires further investigation.


Understanding the impact of multi-drug resistant organism (MDRO) acquisition on renal transplant recipients (RTR) mortality and allograft function is paramount to mitigating deleterious outcomes. Prior studies have been limited by lack of control groups and sample sizes. We aimed to the assess whether the detection of an MDRO or a susceptible organism during the early post-transplant period was associated with increased mortality and allograft failure among RTRs.We performed a retrospective cohort study of RTRs at the Emory University Transplant Center between 2005–2022. Early post-transplant culture positivity was defined as a positive culture within 30 days of renal transplant. The primary outcome was a combined composite of one year- allograft loss and/or mortality following renal transplant. A Kaplan–Meier survival analysis was performed, and differences between survival curves for RTRs with an early post-transplant positive culture (stratified by susceptibility status) and negative control RTRs were assessed using the log-rank test. Multivariable cox proportional hazard and a competing risk analysis were performed.& 2. One hundred and forty-nine (5%) RTRs experienced the composite outcome, this was experienced more frequently among RTRs with an MDRO detected  compared to RTRs with a susceptible organism defected  and negative controls  (Table 3). Significant difference between time from transplantation to the composite outcome when comparing negative controls, MDRO and susceptible organisms RTRs was observed (log rank p < 0.001) . Early post-transplant culture positivity  and MDRO detection  were significantly associated with the composite outcome (Table 4).Among 3,233 RTRs, 259 (8%) had a susceptible organism detected and 35 (1%) had an MDRO detected . Demographic and microbiology characteristics are summarized in Table 1 MDRO as well as susceptible organism acquisition during the early post-transplant period was associated with increased mortality and allograft loss highlighting the need for increased infection prevention efforts within this vulnerable population.All Authors: No reported disclosures.


Cervical carotid dissection is one of the causes of ischemic stroke in young people. Most of the patients with carotid dissection do not have connective tissue diseases . It seems that dissection may occur without an obvious cause or may follow environmental injuries like vigorous neck movements, chiropractic manipulation, emesis, severe coughs, and some infections. We present a case of bilateral carotid dissection in a patient following coronavirus infection and severe coughs.A 38-year-old right-handed man presented with recurrent episodes of transient right hemiparesis and aphasia. He had a history of coronavirus infection and severe persistent, nonproductive cough 7 days before the onset of his symptoms. Carotid angiography showed tapered flame-like appearance in proximal segment of left ICA starting about 2 cm distal to the carotid bulb caused complete occlusion of left ICA and in right CCA angiography there is pseudo aneurysm in right cervical ICA just before the Petrous segment. In 3 months in follow up DSA there is evidence of complete occlusion of right pseudo aneurysm and recanalization of left ICA without stenosis. COVID-19 may have role in the processes that eventually led to CAD Cervical carotid dissection (CAD) is one of the causes of ischemic stroke in young people . AccordiA 38-year-old right-handed man presented to our center complaining of recurrent episodes of transient right hemiparesis and aphasia. The patient had a history of coronavirus infection and severe persistent, nonproductive cough 7 days before the onset of his symptoms. The right-sided symptoms had been occurring two times, each time lasting 10 minutes. His medical history was negative for hypertension, and smoking or recent trauma. On physical examination, the patient was normotensive, intact neurological examination, and no carotid bruits were detectable. Bilateral peripheral pulses were normal and equal. Routine laboratory tests were normal. A computed tomographic (CT) scan and magnetic resonance imaging of the brain was normal. The patient with diagnosis of transient ischemic attack (TIA) was immediately treated with intravenous heparin and oral antiplatelet agents. Carotid angiography showed tapered flame-like appearance in cervical portion of left internal carotid artery (ICA) starting about 2 cm distal to the carotid bulb caused complete occlusion of left ICA . These fLeft vertebral artery angiography revealed collateral circulation to bilateral ICA from bilateral posterior communicating arteries. We decided to treat the patient with simultaneous bilateral carotid artery stenting as he was symptomatic despite receiving medical treatment. A femoral artery approach was obtained and selective bilateral carotid angiogram was performed. The 8F guiding catheter was put to the left CCA and the PILOT 150 micro-guidewire was passed from occluded segment of left ICA after that (8×40 mm) self-expanding carotid stent  was deployed in the ICA. Post-stenting angioplasty was performed with inflation (5×20 mm) NC balloon (Medtronic). We decided to put a stent in right ICA. There was a pseudo-aneurysm in distal cervical portion of ICA. The 8F guiding catheter was introduced to the right CCA and the lesion was crossed by PILOT 150 micro-guidewire and the stent was deployed in the distal cervical portion of ICA.There were no neurological complications. After 3 months in follow up catheter angiography there is evidence of complete occlusion of right pseudo aneurysm and recanalization of left ICA without stenosis .The patient introduced in this case report had spontaneous bilateral cervical carotid dissection with frequent TIA symptoms. It is generally believed that spontaneous dissection occurs in the context of underlying vascular wall structure disorders although no definite arteriopathy is found in many cases . CongeniA positive history of a recent coronavirus infection may be a risk factor for vascular dissection . Two proSome studies found an association between pertussis and CAD. Although difficult to prove, it seems that severe coughs due to pertussis play a role in dissection , 8. Acco Bilateral cervical ICA dissection with sudden onset more probably compromise hemodynamic than atherosclerotic lesions because the collateral circulation has not sufficiently developed. The indication of carotid artery stenting (CAS) for carotid artery dissection is the following situations: (a) symptoms persist or worsen under medical therapy; (b) significant hemodynamic compromise or (c) There is contraindications for antithrombotic therapy . Our pat


The association between family-related life events  and unsustainable working life in terms of unemployment, sickness absence and disability pension (SA/DP) are rarely studied from a life-course perspective although having public health importance. We investigated trajectories of unsustainable working life, and the associations between change in family-related life events and unsustainable working life trajectories by controlling for familial factors.This is a prospective cohort study of 37,867 Swedish twins aged between 20-40 years on 31st December 1994. Data on trajectories of annual unemployment, SA/DP, and a combined measure of unsustainable working life months was collected from the Swedish national registers. The trajectories over a 23-year period were analysed by group-based trajectory modelling. Associations of change in family-related life events with trajectory groups in the whole sample were estimated by multinomial logistic regression and in discordant twin pairs  with conditional models.Most participants had no or low levels of unemployment, SA/DP or combined unsustainable working life during 1994-2016. Individuals who were stably married or changed from being single living without children to married living with children had a decreased risk of unsustainable working life compared to individuals with stable family-related life events. The risk of unsustainable working life months over time was higher among individuals who changed from married to single status regardless of having children (range of HRs:1.31-4.44).Family-related life events such as maintaining the relationship or getting married and having children decreases the risk of unsustainable working life while divorce is a risk factor for unsustainable working life. From a public health perspective, actions to support family formation or life would consequently promote a sustainable working life.• Unsustainable working life was less likely among married and among those who changed from single living without children to married with children compared to those with stable family life events.• Individuals who changed from being married to divorced status had an increased risk of unsustainable working life over time and therefore being potentially an important group for public health.


Aortic dissection is one of the most common emergency condition leading to internal organs or lower limb ischemia and aortic rupture. Herein, we described a reverse “cheese wire” endovascular fenestration repair (CWFER) in a patient with complicated abdominal aortic dissection which had never been reported.A 62-year-old male presented abdominal tear-like pain and acute ischemia of the right lower extremity during the endovascular treatment of celiac trunk aneurysms. Computed tomography angiography (CTA) and digital subtraction angiography (DSA) showed abdominal aortic type B dissection with acute ischemia of the right lower extremity preoperatively. After a detailed preoperative examination, the patient then was performed a reverse CWFER. So far, the patient has been followed-up for 6 months, postoperative CTA demonstrated good stent-graft expansion and perfusion of bilateral common iliac arteries; also, no endoleak was detected.The right iliac artery in this patient supplied by false lumen, which lead to acute ischemia of the right lower extremity, needed to be treated as an emergency and dealt with promptly. CWFER is a very high-risk treatment that requires the rich experience of vascular surgeon and accurate assessment of aortic dissection. After interventional treatment, the patient recovered uneventfully after 6 months’ follow-up.The online version contains supplementary material available at 10.1186/s12893-022-01581-4. B-type aortic dissection is one of the most common emergent conditions affecting the aorta –4. CliniA 62-year-old male presented abdominal tear-like pain and acute ischemia of the right lower extremity during the endovascular treatment of celiac trunk aneurysms. Computed tomography angiography (CTA) and digital subtraction angiography (DSA) showed abdominal aortic type B dissection with acute ischemia of the right lower extremity preoperatively Figs.  and 2, aThis patient provided prior informed consent to this intervention, as well as the publication of the relevant data. Anticoagulation therapy  was prescribed before the patient underwent the procedure. The endovascular repair of abdominal aortic dissection was performed under general anesthesia. The orientation of the puncture was guided by fluoroscopy. The percutaneous access of both femoral arteries was created by placing a 6 F short sheath (Terumo). The gooseneck snare was introduced into the false lumen of the lower abdominal aorta from the left femoral artery under the guidance of the path map. A 0.035-inch guidewire (Terumo) was introduced into the false lumen from the right femoral artery and captured by the gooseneck snare, an additional movie file shows this in more detail (see Additional file A gentle upward bilateral pull was maneuvered using a ‘‘cheese wire’’ technique to shear the flap of the mid-abdominal aorta from the distal tear of the left common iliac artery dissection up to the proximal end Fig. . This opAngiography confirmed the patency of the bilateral common iliac arteries and adequate visceral perfusion with no evidence of endoleak or arterial rupture Figs.  and 4. TThe open surgery of type B aortic dissection is still associated with significant morbidity and mortality . The AorThis patient had symptoms of acute right iliac artery occlusion, such as severe pain in the right lower extremity and no pulse. Previous studies demonstrated the feasibility of using intravascular fenestration of dissection flap for treating poor perfusion secondary to acute aortic dissection –10. ChalThis would establish the true-false-true through wire access by maintaining the Lunderquist wire and sheath access to the true lumen on both sides. Completion angiography demonstrated excellent technical results with no evidence of endoleak and a satisfactory apposition of the graft to the aortic wall at the proximal neck. Also, the 6-month follow-up did not show an endoleak on CT angiography, and the patient reported to be feeling well. Taken together, the cheese-wire technique is a useful maneuver that facilitates endovascular arterial dissection repair. Adequate proximal or distal fixation could be conducted by endovascular fenestration. Nonetheless, sufficient experience is necessary for interventional therapy; also, total percutaneous approach is considered feasible for treating some sophisticated aortic dissections.Additional file 1. The procedure of reverse “cheese wire” endovascular fenestration repair.Additional file 2. Angiography confirmed the patency of the bilateral common iliac arteries and adequate visceral perfusion.


DNA methylation at the fifth position of cytosine (5mC) is one of the most studied epigenetic mechanisms essential for the control of gene expression and for many other biological processes including genomic imprinting, X chromosome inactivation and genome stability. Over the last years, accumulating evidence suggest that DNA methylation is a highly dynamic mechanism driven by a balance between methylation by DNMTs and TET-mediated demethylation processes. However, one of the main challenges is to understand the dynamics underlying steady state DNA methylation levels. In this review article, we give an overview of the latest advances highlighting DNA methylation as a dynamic cycling process with a continuous turnover of cytosine modifications. We describe the cooperative actions of DNMT and TET enzymes which combine with many additional parameters including chromatin environment and protein partners to govern 5mC turnover. We also discuss how mathematical models can be used to address variable methylation levels during development and explain cell-type epigenetic heterogeneity locally but also at the genome scale. Finally, we review the therapeutic implications of these discoveries with the use of both epigenetic clocks as predictors and the development of epidrugs that target the DNA methylation/demethylation machinery. Together, these discoveries unveil with unprecedented detail how dynamic is DNA methylation during development, underlying the establishment of heterogeneous DNA methylation landscapes which could be altered in aging, diseases and cancer. In mammOver the last years DNA (de)methylation has been widely investigated thanks to high throughput technological advances, thus allowing methylome profiling of a large panel of biological samples. Accumulating evidence suggest that DNA methylation is a highly dynamic mechanism driven by a balance between methylation and demethylation processes. However, although the distribution of DNA methylation in the genome is now well-documented at steady state, the dynamics of the underlying mechanisms requires more attention. In this review article, we will first give an overview of the latest advances highlighting DNA methylation as a dynamic cycling process with a constant turnover of cytosine modifications. We will also discuss how variable methylation levels could explain the epigenetic heterogeneity observed during early embryo development in mammals and might influence cellular differentiation.Arabidopsis thaliana, active replacement of 5mCs by unmodified cytosines is initiated by the glycosylase activity of Demeter (DME)/repressor of silencing 1 (ROS1) enzymes from the base excision repair (BER) machinery  and the BER machinery during estrogen receptor-mediated transcription activation . HoweverDNMT1 is responsible for the maintenance of DNA methylation patterns during DNA replication. The multifunctional protein UHRF1 has been reported to act as an important cofactor of DNMT1 in DNA maintenance methylation . UHRF1 iImpairment of DNA maintenance methylation reduces global DNA methylation and results in passive demethylation characterized by a progressive dilution and loss of 5 mC marks during successive DNA replication cycles. Several processes can be involved in replication-dependent passive DNA demethylation including the downregulation of DNMT1/UHRF1 complex , the impDNA methylation patterns are essential for cell fate decisions during mammalian development and act as epigenetic barriers by limiting the developmental potential of cells and restricting their differentiation to avoid a regression into an undifferentiated state. Although DNA methylation landscapes are stably maintained in somatic cells, the genome undergoes a dynamic two-step genome wide reprogramming . First, de novo methylation and demethylation, and the functions of the regulators have been largely studied using mouse and human embryonic stem cells (mESCs and hESCs) as powerful model systems for both in vivo and in vitro assays. Both mESCs and hESCs derive from the inner cell mass of blastocyst-stage pre-implantation embryos but hESCs reflect a later phase in development than mESCs in addition to having distinct biological properties methylation dynamics plays a key role in the spatio-temporal regulation of gene expression, the maintenance of genome stability and embryonic development . The delde novo methylation during development is also observed in DNMT3s DKO mESCs as well as in mouse early embryos deficient in both of DNMT3A and DNMT3B, which leads to embryonic lethality  to form the fundamental unit of chromatin: the nucleosome . Each nuDynamic DNA methylation landscapes are shaped by a local competition between TETs and DNMTs for CGI association as well as other proteins partners such as TFs. Actually, DNA methylation and TFs binding act in a synergistic manner to regulate the spatio temporal expression of genes and chromatin remodeling, leading to local DNA methylation changes. Zinc finger cysteine-X-X-cysteine (ZF-CXXC) domain-containing proteins specifically target unmethylated CpGs at CGIs which are commonly hypomethylated and where they have chromatin-modifying activities . The firEmerging evidence suggest the existence of long non-coding RNA (lncRNA)-mediated DNA methylation. LncRNAs are transcripts with a length over 200 nucleotides which have been shown to interact with DNMTs and TETs through different mechanisms . Methylade novo and maintenance DNMTs. These models were then further improved by Genereux et al.  involved in establishing cell-type specific heterogeneity. A classical model of methylation dynamics has been first proposed by Otto and Walbot  and Pfeix et al.  and assupG dyads , they espG dyads . By usinpG dyads . Numeroun levels .The developed mathematical models explained the dynamics underlying steady state DNA methylation levels. For years, bulk cell measurements approaches used the average DNA methylation level of a cell population to define the methylation state of CpGs without considering that each CpG may exist in a dual state (methylated or unmethylated). The development of high-resolution single-cell approaches and especially single cell whole genome Bisulfite Sequencing (scBS-Seq) largely contributed to unravel DNA methylation variations in differentiating cells, at the genome scale. Using whole genome scBS-Seq, several studies demonstrated the emergence of methylation heterogeneity in mESCs. Howeverin vitro and in vivo methylation enzymes revealed highly dynamic methylation changes in early development both  in vivo . The co- in vivo . By cons in vivo .de novo methylation  resulting in their silencing as well as proto-oncogenes overexpression are also frequently observed. Aberrant DNA methylation leads to the formation and/or progression of cancer including hematological malignancies and solid tumors  and methWithin the last years, based on the reversible nature of epigenetic marks, small molecules referred to as epidrugs were developed to target epigenetic regulators . Aberranl-tryptophan 1 (RG108)) were designed to improve cancer treatments. MG98 is an antisense oligonucleotide targeting DNMT1 messenger RNA (mRNA) but, despite specifically downregulating DNMT1 in a dose-dependent manner, controversial responses have been observed in different (pre)clinical trials  promotes DNA demethylation by TETs which makes it a promising therapeutic agent that could be used to increase 5 mC turnover through TET activation. Indeed, Vitamin C is a well-studied antioxidant known to work as a co-factor for Fe(II) 2-oxoglutarate dioxygenase enzymes like TET enzymes . By reduIn silico screening of natural products as potential TET inhibitors further identified compound 35 (C35), a catechol containing small molecule targeting the catalytic core of TETs and thus blocking their enzymatic activity  reprogramming by Yamanaka et al., in 2006, allowed to generate pluripotent cells from differentiated somatic cells . Indeed, studies . AltogetFor the last decades, emerging high-throughput technological advances and mathematical modelling largely contributed to unravel DNA methylation oscillations at both local and genome scales. DNA methylation has been highlighted as a dynamic cycling process regulated by a balance between DNMTs and TETs and associated with a constant turnover of cytosine modifications. These variable steady state DNA methylation levels generate heterogenous DNA methylation patterns in healthy cells but also in cancer cells. Driven by DNA methylation dynamics, tumor heterogeneity can act as a barrier in cancer treatment by supporting tumor cells progression. Within the last years, DNA methylation has been increasingly investigated as a potential biomarker and therapeutic target for human cancer treatment. DNA methylation-based epigenetic clocks have been developed as diagnostic tools and age prediction biomarkers, while transient reprogramming strategies reinforced our comprehension of DNA methylation dynamics to design new therapies. Several molecules targeting methylating (DNMTs) and demethylating (TETs) enzymes were identified as potential anticancer drugs through modulations of DNA methylation dynamics. While some epidrugs are currently used alone or in combination with other therapies for cancer treatment, one of the main challenges remains to reduce side effects and cytotoxicity to ensure a positive outcome for patients.


A 69-year-old man with non-ischemic cardiomyopathy and permanent atrial fibrillation underwent a pacemaker upgrade to a cardiac resynchronization therapy (CRT) defibrillator several years earlier. He experienced multiple inappropriate ICD shocks due to lead fracture and underwent a lead extraction with insertion of a new ICD lead performed at an outside hospital. Following the lead revision, the patient developed worsening heart failure, as well as intermittent pocket stimulation. An echocardiogram demonstrated a left ventricular (LV) ejection fraction of 35%, which was markedly reduced from the prior echocardiogram. He presented 1 year later for an elective defibrillator generator replacement due to battery depletion. His chest X-ray showed a rightward and inferior displacement of the ICD lead as compared to the pacemaker leads (panel A in Fig. This case illustrated a spectacular complication of a trans-arterial placement of the ICD lead into the aortic arch and a unique cause of CRT failure, with epicardial and endocardial pacing across the lateral LV wall. Although inadvertent arterial puncture can occur during routine access using the subclavian or proximal axillary vein , an LV l


Apical hypertrophic cardiomyopathy (ApHCM) is a clinical challenge when presenting with symptoms of angina plus shortness of breath. An appropriate diagnosis of concurrent coronary artery disease (CAD) is needed for proper diagnosis, risk stratification, and management. We present a case of a 64-year-old gentleman with a history of ApHCM and CAD with previous percutaneous intervention presenting with recurrent angina. A repeat coronary angiography showed no new obstructive lesions. A stress cardiac magnetic resonance imaging was performed, which showed perfusion defect in the apex with apical scarring likely secondary to microvascular disease. The patient was managed medically with the improvement of symptoms. Diagnosis and management of CAD in patients with ApHCM are challenging. Multiple diagnostic modalities may be required for delineating the underlying pathology. Patients should be managed initially with medications. If symptoms are not controlled with medical management, a heart team approach with referral to an advanced center experienced in apical myectomy should be considered. One of the rare variants of hypertrophic cardiomyopathy is apical hypertrophic cardiomyopathy (ApHCM) which mainly affects the left ventricular apex. Most patients with this morphology present with midventricular obstruction rather than left ventricular outflow tract obstruction (LVOTO). Based on some research studies, it has been found that ApHCM is mostly prevalent in the East Asian population ,2. ApHCMA 64-year-old male with a past medical history of coronary artery disease (CAD) and ApHCM presented to the cardiology clinic with recurrent exertional chest pain. He had undergone coronary angiography 10 months previously for angina, which documented 80% stenosis of the first posterolateral branch of the right coronary artery (RCA) with the subsequent percutaneous intervention of the lesion. Symptoms of chest pain initially improved but recurred in the four months before his clinic follow-up and were described as central non-radiating chest discomfort on minimal exertion that typically resolved with rest. Repeat electrocardiogram (ECG) showed left ventricular (LV) hypertrophy with deep T wave inversion in V3, unchanged from previous ECG and attributed to known ApHCM  was noted to have a mild diffuse plaque with maximal 30% stenosis and to be shorter compared to the diagonal Figure . RCA shoLeft ventricular end-diastolic pressure was elevated (21 mmHg), and the left ventriculogram showed typical findings of ApHCM Figure .Subsequent stress cardiac magnetic resonance imaging (MRI) confirmed severe apical hypertrophy Figure  and multGiven MRI findings, his angina symptoms were attributed to microvascular ischemia of the apex secondary to severe ApHCM. The patient was given pharmacological treatment with beta-blockers (BB) and calcium channel blockers (CCB) and showed subsequent improvement.ApHCM is a variant of hypertrophic cardiomyopathy (HCM) characterized by isolated hypertrophy of the LV apex. ApHCM accounts for 3-10% of all HCM in the United States compared to 25% of all HCM cases in Japan . The resThe evaluation includes an ECG and an echocardiogram, which show high QRS voltage and symmetrical deep T waves in the left precordial leads and increased apical wall thickness of more than 15 mm . CoronarMedical management is similar to therapy for HCM. BBs are the backbone of the treatment . CCBs arSome patients have shown improved symptoms with the novel surgical technique of apical myectomy ,16. AlcoPatients with ApHCM can present with angina, which poses a diagnostic dilemma of whether symptoms are caused by concomitant coronary disease. Careful patient evaluation with angiography and perfusion imaging helps delineate the underlying pathology and permits more specific treatment and risk stratification because patients with concurrent CAD have a worse prognosis.


Culex mosquito populations near (10 m) and far (150 m) from each coop location for the peak WNV transmission season (Jul-Sep 2019). We also monitored serum IVM levels in treated chickens and tested for WNV antibodies in all chickens throughout the study. RESULTS/ANTICIPATED RESULTS: Since IVM impacts only mosquitoes that live long enough to take a bloodmeal from a treated chicken, we do not expect to find a marked difference in adult Culex abundance between the two treatment arms, but we expect to find a reduction in WNV infection prevalence and a shift in female mosquito age structure towards younger, uninfected individuals at treated coops. We also anticipate seroconversions in treated chickens to occur at lower rates versus untreated control chickens indicating a reduction in WNV transmission intensity at treated coops. We observed no negative health outcomes from the long-term ingestion of IVM by study chickens. A pathological investigation is underway to compare histological findings between treated and untreated chickens. DISCUSSION/SIGNIFICANCE OF IMPACT: IVM provides the potential for targeted mosquito control. Reduced WNV transmission dynamics here is a stepping stone to a commercial WNV control strategy; IVM-treated feed for wild birds for homeowners’ use to combat WNV transmission in their neighborhoods.OBJECTIVES/GOALS: We conducted a randomized field trail to evaluate the efficacy and safety of a novel vector control strategy that involves treating urban backyard chickens with ivermectin (IVM), a widely used antiparasitic and mosquitocial drug. The goal was to reduce vector mosquito populations and West Nile virus (WNV) transmission. METHODS/STUDY POPULATION: We placed eight flocks—four treated and four untreated control—of six Lohmann brown chickens (16 month-old) each in backyard coops across Davis, CA and administered IVM in feed daily at treated coops (200 mg IVM/kg feed) for eleven weeks. We monitored entomological indices weekly  in


Anodal capture can provide a resynchronization effect on biventricular pacing. However, evidence of such an effect remains unclear in left bundle branch pacing (LBBP). We report a patient with a baseline sinus rhythm with complete atrioventricular block and a ventricular escape rhythm with a right bundle branch (RBB) block QRS morphology and left axis deviation who received LBBP for cardiac resynchronization therapy (CRT), and its anodal capture stimulation (ANS) rendered a near-normal QRS morphology. The resolution of the RBB pattern during bipolar pacing in this patient resulted from a fusion of LBBP and right ventricular septal capture from ANS. In conclusion, CRT can be achieved during LBBP by ANS in patients who do not have retrograde RBB activation. Left bundle branch (LBB) pacing (LBBP) is increasingly being performed, especially in patients with high-grade degree atrioventricular block (AVB), to avoid complications related to non-physiologic ventricular depolarization from pure myocardial pacing. Anodal capture has been demonstrated to have beneficial effects on cardiac resynchronization therapy (CRT) with biventricular pacing. However, there is still a lack of data on the effect of anodal capture in LBBP.. His-bundle lead placement was attempted but was unsuccessful due to the absence of the His-bundle potential. LBBP lead placement was then performed as described by Wu et al.1A 67-year-old woman presented for an elective upgrade from a dual-chamber pacemaker to a cardiac resynchronization therapy defibrillator (CRT-D) due to pacing-induced left ventricular (LV) systolic dysfunction. Her past medical history was significant for her complete heart block status after a dual-chamber permanent pacemaker implant, coronary artery disease status after coronary artery bypass graft surgery, and hypertension. Her baseline electrocardiogram (ECG) showed normal sinus rhythm with complete heart block. She had an escape rhythm with a right bundle branch (RBB) block morphology with a QRS duration of 121 ms and a left axis deviation (LAD) at a rate of 30 bpm Figure 1 shows a set of surface ECG tracings from baseline to pacing at different sites during lead advancement. Her baseline ventricular escape rhythm most likely originated either from the left posterior fascicle or LBB with underlying left anterior fascicular block given the absence of the His-bundle potential and right bundle branch (RBB) block–LAD QRS morphology. Unipolar pacing at the target site for the LBB on the right ventricular (RV) septal area demonstrated a typical “W” pattern in V1 . The lead was rapidly rotated clockwise until the tip penetrated the septal surface and reached the mid-septal area. The paced QRS morphology at this site demonstrated that the notch in lead V1 moved toward the end of the QRS complex . Further lead advancement resulted in a more prominent R-wave on the paced QRS morphology in lead V1. As the tip of the lead reached the LBB area , the paced QRS morphology showed an RBB pattern with LAD , which was similar to the baseline QRS morphology indicating LBB or left posterior fascicle capture. There were no changes in QRS morphology during decremental unipolar pacing at this site, starting from 5.0 V at 0.5 ms to complete loss of capture at 0.8 V at 0.5 ms. After the delivery sheath was pulled back and the ring electrode was exposed, a repeat decremental pacing in a bipolar configuration was performed at 5.0 V at 0.5 ms. Paced QRS morphology at a high output resulted in a narrower QRS width and the resolution of the RBB pattern . As the pacing output was decreased to 3.0 V at 0.5 ms, the QRS morphology changed to an RBB pattern with a wider QRS width similar to the baseline QRS morphology and unipolar paced QRS morphology.2 which is the ring electrode in this bipolar configuration. Capture usually occurs at the tip electrode (cathode) and requires a lesser pacing output than ANS. ANS can also be observed in CRT devices that allow pacing from the LV lead electrode as a cathode to the RV lead ring or coil as an anode. ANS from the RV lead electrode can result in biventricular capture during LV pacing alone or triple-site ventricular capture during biventricular pacing.4 In summary, CRT can be achieved during LBBP by ANS in patients who do not have retrograde RBB activation. However, the benefit of CRT from ANS in LBBP is unclear and requires more clinical studies.CRT with a near-normal QRS complex can be achieved during LBBP by a retrograde RBB activation in some patients. However, this patient did not have a retrograde RBB activation as demonstrated by there being no resolution of RBB block morphology during unipolar pacing. The narrow QRS morphology with a near-normal QRS morphology during bipolar pacing in this patient resulted from a fusion of LBBP and RV septal capture from anodal stimulation (ANS). ANS is defined as a capture at the anode,


Branch vessel occlusion is a major cause of stroke in parent artery sacrifice (PAS) for vertebral artery dissecting aneurysms (VADA). There is now an increasing trend towards preservation of branch vessels during PAS. Stents are commonly employed to achieve this but bring with it the attendant risks of future thrombosis and lifelong antiplatelet use. Although a microcatheter protection technique has been utilised in branch artery protection of wide-necked saccular aneurysms, it has rarely been described in PAS for VADAs. We describe the use of a dual microcatheter technique in the protection and remodelling of the posterior inferior cerebellar artery (PICA) during PAS of the vertebral artery, which also served as a temporary scaffold to support placement of the coils during the embolisation process. Parent artery sacrifice (PAS) for vertebral artery dissecting aneurysms (VADAs) is a well-established technique ; the priA microcatheter protection technique is one of the described assisted techniques used to preserve parent or branch arteries in endovascular embolisation of wide-necked saccular aneurysm; however, this technique is rarely employed in embolisation of VADAs. We describe the technique of microcatheter protection of the PICA during PAS of a VADA resulting in complete occlusion of the vertebral artery while simultaneously preserving the adjacent PICA, without the use of a stent or flow diverter. A 57-year-old woman presented with a World Federation of Neurosurgical Societies Grade III, Modified Fisher Grade IV subarachnoid haemorrhage. Computed tomographic angiography (CTA) showed a right VADA affecting the proximal V4 segment.Catheter digital subtraction angiogram confirmed a 5.3 x 11.5 mm (diameter x length) dissecting aneurysm Figure  involvinA right transfemoral approach was used to insert a 6-Fr guiding catheter into the cervical vertebral artery. After choosing the best working projection by using a biplane angiography unit (GE innova 3131-IQ), a roadmapping technique was done.A 1.7-Fr microcatheter  was advanced to the right vertebral artery aneurysm. A 2.3-Fr microcatheter  was then inserted in tandem, and was used to cannulate the PICA Figure . Under sFollow-up CTA Figure  showed cThe technique of microcatheter protection of the PICA has been described in angioplasty of atherosclerotic intracranial lesions  and in tIn our case, preservation of the PICA to minimize complications of side branch occlusion was important because of its larger-than-normal calibre and presumed larger vascular territory. Moreover, there was angiographic absence of collateral supply either from an ipsilateral AICA-PICA complex or contralateral bihemispheric PICA disposition. Its larger-than-normal calibre also facilitated temporary cannulation with a microcatheter to enable reconstruction of the PICA into an end vessel while the parent artery was being occluded. This technique avoids the use of stents, reducing costs and obviating the need for periprocedural and lifelong antiplatelet therapy. The risk of delayed stent occlusion in the PICA is also eliminated. Cannulation of the PICA also serves as a means of remodelling for the reconstruction of the PICA origin and provides mechanical stabilisation to enable better packing of the coils in the dissected segment, reducing the risk of recurrence. This is achievable even with the higher coil mass needed for parent artery occlusion.Branch artery protection without the use of stents is feasible in selected cases where the vessel origin is just adjacent to (but not within) the diseased segment. This ameliorates the morbidity of procedure-related infarcts while eliminating stent-related complications. This technique is also applicable in VADAs proximal to the PICA origin where the microcatheter can be introduced via the contralateral vertebral artery.


The growth of solo living has important implications for the rising “loneliness epidemic” among older adults. This study considers whether two forms of social connectedness—extra-household core discussion networks and formal social participation—buffer the loneliness associated with living alone. Our study uses data from two surveys  encompassing 20 developed Western countries in 2009/2010 and 2015/2016 . Harmonizing measures across data sets, we estimate survey-specific and pooled linear regression models with interaction terms. Results indicated that high levels of social connectedness only moderately buffer the loneliness associated with living alone in later life. Findings were largely consistent across regions of Europe and the United States, though the buffering patterns were most robustly identified for widowed solo dwellers. Taken together, the results suggest that extra-household connections are partial compensators, but do not seem to fully replace the ready companionship afforded by residential co-presence in later life. Future research is needed to understand whether the efficacy of compensatory connections differs by gender, race/ethnicity, and across more diverse global regions.


The authors should be congratulated on reporting their findings in a large radical cystectomy cohort for muscle-invasive (MIBC) and metastatic bladder cancer . The man


Millions of older adults living in close communal contact in senior housing communities remain vulnerable during the COVID-19 pandemic. Approximately 30% of Lifestyle Leaders currently live in senior housing. This presentation will cover the unique challenges these participants have encountered, including experiences with and the impact of changing norms and pandemic-related policies within communities over time. In March 2020, 75% of Lifestyle Leaders rated the response of their senior housing community to COVID-19 as “Excellent” or “Very Good.” In August 2020, they reported they believed they were less likely to contract COVID-19 living in senior housing compared to people not living in senior housing (80%). Interview data revealed Lifestyle Leaders in these environments held favorable views toward their communities. This presentation will further discuss how the Lifestyle Leaders who do not live in senior housing perceive senior living and how these perceptions have shifted during the pandemic.