Vascular Endothelial Growth Factor-C Treatment Enhances Cerebrospinal Fluid Outflow during Toxoplasma gondii Brain Infection but Does Not Improve Cerebral Edema.

Cerebral edema frequently develops in the setting of brain infection and can contribute to elevated intracranial pressure, a medical emergency. How excess fluid is cleared from the brain is not well understood. Previous studies have shown that interstitial fluid is transported out of the brain along perivascular channels that collect into the cerebrospinal fluid (CSF)-filled subarachnoid space. CSF is then removed from the central nervous system through venous and lymphatic routes. The current study tested the hypothesis that increasing lymphatic drainage of CSF would promote clearance of cerebral edema fluid during infection with the neurotropic parasite Toxoplasma gondii. Fluorescent microscopy and magnetic resonance imaging was used to show that C57BL/6 mice develop vasogenic edema 4 to 5 weeks after infection with T. gondii. Tracer experiments were used to evaluate how brain infection affects meningeal lymphatic function, which demonstrated a decreased rate in CSF outflow in T. gondii-infected mice. Next, mice were treated with a vascular endothelial growth factor (VEGF)-C-expressing viral vector, which induced meningeal lymphangiogenesis and improved CSF outflow in chronically infected mice. No difference in cerebral edema was observed between mice that received VEGF-C and those that rececived sham treatment. Therefore, although VEGF-C treatment can improve lymphatic outflow in mice infected with T. gondii, this effect does not lead to increased clearance of edema fluid from the brains of these mice.

Activated prothrombin complex concentrate to treat bleeding events in acquired hemophilia A: BAHAS study.

OBJECTIVE: Activated prothrombin complex concentrate (aPCC) is a bypassing agent indicated to treat bleeds in patients with acquired hemophilia A (AHA). Nevertheless, its efficacy and safety in the real-world setting have not often been addressed. METHODS: We report the experience of Spanish reference centers for coagulation disorders and from acquired hemophilia Spanish Registry (AHASR) from August 2012 to February 2021. Follow-up period of 30 days after aPCC withdrawal. RESULTS: Thirty patients with a median age of 70 years old, suffering from 51 bleeds treated with aPCC were finally evaluated. As first-line treatment, aPCC stopped bleeding in 13 of 14 (92.9%) cases. aPCC as the second line after recombinant factor VIIa failure, stopped bleeding in all cases. In 17 patients, aPCC was used far from initial bleed control as prophylaxis of rebleeding with 94% effectiveness. No thromboembolic episodes were communicated. One patient developed hypofibrinogenemia, which did not prevent aPCC from halting bleeding. No other serious adverse events possibly or probably associated with aPCC were reported. CONCLUSIONS: This data support aPCC as hemostatic treatment in AHA with high effectiveness and excellent safety profile in acute bleeds and as extended use to prevent rebleedings, even in aging people with high cardiovascular risk.

Early experience of aortic surgery during the COVID-19 pandemic in the UK: A multicentre study.

BACKGROUND: A significant restructuring of the healthcare services has taken place since the declaration of the coronavirus disease 2019 (COVID-19) pandemic, with elective surgery put on hold to concentrate intensive care resources to treat COVID-19 as well as to protect patients who are waiting for relatively low risk surgery from exposure to potentially infected hospital environment. METHODS: Multicentre study, with 19 participating centers, to define the impact of the pandemic on the provision of aortovascular services and patients' outcomes after having adapted the thresholds for intervention to guarantee access to treatment for emergency and urgent conditions. Retrospective analysis of prospectively collected data, including all patients with aortovascular conditions admitted for surgical or conservative treatment from the 1st March to the 20th May 2020. RESULTS: A total of 189 patients were analyzed, and 182 underwent surgery. Diagnosis included: aneurysm (45%), acute aortic syndrome (44%), pseudoaneurysm (4%), aortic valve endocarditis (4%), and other (3%). Timing for surgery was: emergency (40%), urgent (34%), or elective (26%). In-hospital mortality was 12%. Thirteen patients were diagnosed with COVID-19 during the peri-operative period, and this subgroup was not associated with a higher mortality. CONCLUSIONS: There was a significant change in service provision for aortovascular patients in the UK. Although the emergency and urgent surgical activity were maintained, elective treatment was minimal during early months of the pandemic. The preoperative COVID-19 screening protocol, combined with self-isolation and shielding, contributed to the low incidence of COVID-19 in our series and a mortality similar to that of pre-pandemic outcomes.

Turn down of acute aortic syndrome cases during COVID-19: Results from UK multicentre studies.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has restructured the healthcare systems, prioritizing resources to treat COVID-19 patients. The aim of this study was to establish if patients affected by acute aortic syndrome (AAS) had unrestricted access to emergency treatment and evaluate outcome of these patients during the peak of the pandemic. METHODS: This is a retrospective analysis of prospectively collected data between March and June 2020 from 19 participating cardiac surgery centers in the United Kingdom. RESULTS: Among 95 patients who presented with an AAS in the participating centers; 85 (89%) underwent surgery, 7 (7%) were turned down for surgery because of their profile of comorbidities, and 3 (3%) died on transfer. Among the patients treated conservatively, three of them (43%) were alive at 30 days. We observed no significant restriction in access to treatment for AAS during the early months of the pandemic. CONCLUSION: Services for life-threatening aortic surgery patients were maintained during the COVID-19 period through patient selection and timing of surgery. The rate of surgical turn-down was comparable to published figures despite the challenges faced during the COVID-19 pandemic.

Type A aortic syndromes in COVID-19 positive patients: Case series from a UK multicentre study.

OBJECTIVE: The coronavirus disease (COVID-19) increases the respiratory complications and carries a higher mortality in the immediate postoperative period. The aim of this study was to analyze the outcomes of patients with type A acute aortic syndromes (AAS) diagnosed with COVID-19 in the perioperative period. METHODS: Retrospective analysis of prospectively collected data between March and August 2020 from 20 participating cardiac surgery centers in the United Kingdom. RESULTS: Among 122 patients who underwent emergency surgical repair for type A AAS at the participating centers, 3 patients (2.5%) tested positive for COVID-19 in the preoperative screeing, and 4 cases turned to be positive in the postoperative period having been operated on an unknown COVID-19 status. Another patient was diagnosed of COVID-19 disease based on radiological features. These eight patients had increased postoperative complications, including respiratory failure, longer ventilation times, and Intensive Therapy Unit (ITU) stay and increased mortality when compared with COVID-19 negative patients. CONCLUSION: COVID-19 disease in the perioperative period of type A AAS poses a challenge. Despite the increasing morbidity and mortality associated with the virus, the prognosis of the aortic disease is poorer and emergency surgery should not be contraindicated based on the COVID-19 diagnosis alone.

Cardiac surgery in patients with confirmed COVID-19 infection: Early experience.

The novel coronavirus, now termed SARS-CoV-2, has caused a significant global impact in the space of 4 months. Almost all elective cardiac surgical operations have been postponed in order to reduce transmission and to allocate resources adequately. Urgent and emergency cardiac surgery is still taking place during the pandemic. The decision to operate in urgent patients with active/recent COVID-19 infection is difficult to make, particularly as it is still an unknown disease entity in the setting of emergent cardiac surgery. We present a case series of three patients who underwent urgent cardiac surgery and who have had recent or active COVID-19 infection.

The Pan London Emergency Cardiac Surgery service: Coordinating a response to the COVID-19 pandemic.

Over the last 4 months, the novel coronavirus, SARS-CoV-2, has caused a significant economic, political, and public health impact on a global scale. The natural history of the disease and surge in the need for invasive ventilation has required the provision of intensive care beds in London to be reallocated. NHS England have proposed the formation of a Pan-London Emergency Cardiac surgery (PLECS) service to provide urgent and emergency cardiac surgery for the whole of London. In this initial report, we outline our experience of setting up and delivering a pan-regional service for the delivery of urgent and emergency cardiac surgery with a focus on maintaining a COVID-free in-hospital environment. In doing so, we hope that other regions can use this as a starting point in developing their own region-specific pathways if the spread of coronavirus necessitates similar measures be put in place across the United Kingdom.

Valve Replacement for Moderate Aortic Stenosis in Octogenarians Undergoing Revascularization.

BACKGROUND AND AIM OF THE STUDY: The study aim was to determine if the 'prophylactic' replacement of the aortic valve to treat moderate aortic valve stenosis (AS) in octogenarians undergoing cardiac surgery for coronary disease can influence outcome, and is also justified. METHODS: In a retrospective analysis of octogenarians operated on at the authors' center between 1998 and 2012, the patients were allocated to: Group I, isolated coronary artery bypass graft surgery (CABG; n = 159); Group II, combined CABG and aortic valve replacement (AVR) with the primary indication for surgery being severe AS (n = 156); and Group III, combined AVR +CABG with coronary disease being the primary indication and concomitant 'prophylactic' AVR (n = 34). RESULTS: The hospital mortality for octogenarians undergoing CABG+AVR was 8% compared to 2% for isolated CABG (p = 0.02). Survival at one year was higher in the isolated CABG group (94%) than in the CABG+AVR group (86%) (p = 0.01), but was no different at five years. Mortality according to AVR indication was similar (Group II 8% versus Group III 9%), as was one- and five-year survival. Group III had a higher preoperative co-morbid risk profile, including logistic EuroSCORE 21.7% versus 18% in Group II (p = 0.05), more recent myocardial infarctions, previous percutaneous interventions, peripheral vascular disease, and poor left ventricular function. Long-term symptomatic relief was excellent in Group III. Patients whose predominant disease profile was ischemic (Groups I and III) had a higher long-term risk of recurrent angina and stroke. CONCLUSION: In-hospital mortality is higher for octogenarians undergoing CABG+AVR compared to those undergoing isolated CABG. In the present study, a 'prophylactic' AVR was justified in patients with moderate AS, and their increased mortality (versus isolated CABG) was congruent with a higher preoperative co-morbid risk profile. Excellent long- term symptom-free survival further justifies 'prophylactic' AVR in octogenarians undergoing CABG with coexistent moderate AS.

Biomonitoring exposure assessment to contemporary pesticides in a school children population of Spain.

The exposure to pesticides amongst school-aged children (6-11 years old) was assessed in this study. One hundred twenty-five volunteer children were selected from two public schools located in an agricultural and in an urban area of Valencia Region, Spain. Twenty pesticide metabolites were analyzed in children's urine as biomarkers of exposure to organophosphate (OP) insecticides, synthetic pyrethroid insecticides, and herbicides. These data were combined with a survey to evaluate the main predictors of pesticide exposure in the children's population. A total of 15 metabolites were present in the urine samples with detection frequencies (DF) ranging from 5% to 86%. The most frequently detected metabolites with DF>53%, were 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of chlorpyrifos), diethyl phosphate (DEP, generic metabolite of OP insecticides), 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPY, metabolite of diazinon) and para-nitrophenol (PNP, metabolite of parathion and methyl parathion). The calculated geometric means ranged from 0.47 to 3.36 µg/g creatinine, with TCPy and IMPY showing the higher mean concentrations. Statistical significant differences were found between exposure subgroups (Mann-Whitney test, p<0.05) for TCPy, DEP, and IMPY. Children living in the agricultural area had significantly higher concentrations of DEP than those living in the urban area. In contrast, children aged 6-8 years from the urban area, showed statistically higher IMPY levels than those from agricultural area. Higher levels of TCPy were also found in children with high consumption of vegetables and higher levels of DEP in children whose parents did not have university degree studies. The multivariable regression analysis showed that age, vegetable consumption, and residential use of pesticides were predictors of exposure for TCPy, and IMPY; whereas location and vegetable consumption were factors associated with DEP concentrations. Creatinine concentrations were the most important predictors of urinary TCPy and PNP metabolites.

Inflammation in aortic surgery: postoperative evolution of biomarkers according pathologies and segments of the aorta.

OBJECTIVES: Aortic pathologies often present with elevated inflammatory biomarkers due to the nature of the disease. Open aortic surgery causes significant trauma to the body due to often mandatory ischemic periods, long cardiopulmonary bypass times and polytransfusion. We aim to determine postoperative trends on inflammation biomarkers for different aortic pathologies and type of surgery in different segments of the aorta. METHODS: Retrospective review of prospectively collected data of 193 consecutive patients who underwent aortic surgery in our centre between 2017 and 2021, grouped according to the type of aortic intervention: (1) Type A aortic dissection (AD) repair with ascending aorta/hemiarch replacement, (2) Aortic root replacement (ARR), (3) Aortic arch + Frozen elephant trunk (FET), (4) Descending thoracic aorta (DTA)/Thoraco-Abdominal aortic repair (TAA). Primary outcomes were daily values of white blood cells (WBC) and C-Reactive Protein (CRP) during the first 15 postoperative days. RESULTS: All groups had a similar inflammatory peak in the first 2-4 days (WBC 12-15 × 109 c/L). AD and FET groups show similar trends with WBC and CRP peaks on days 2 and 10. The ARR group didn't experience the 2nd peak as most patients were already discharged. DTA/TAA patients experienced a more prolonged inflammatory response, reaching a plateau by day 5-10. AD group shows the highest WBC levels and the DTA/TAAA group the highest CRP levels. CRP levels remain elevated (100-200 mg/L) in all groups after 15 postoperative days. CONCLUSIONS: Inflammatory biomarkers show different postoperative trends depending on the clinical presentation and complexity of the aortic procedure performed. Further understanding of the inflammatory response to different aortic pathologies and surgical procedures will permit reduction on the liberal use of antibiotics that this cohort of patients are usually exposed to. An earlier version of the data included in this manuscript was presented as Oral Abstract in the UK Society of Cardiothoracic Surgery Annual meeting in 2021.

Thrombotic risk and features of patients with inferior vena cava agenesis: a multicentre, retrospective, observational study.

BACKGROUND: Inferior vena cava agenesis (IVCA) is a rare anomaly predisposing affected people to lower-limb venous thrombosis with low frequency of pulmonary embolism. Antenatal thrombosis and inherited thrombophilia have been suggested as causes of IVCA. However, there is little evidence on the clinical course and management of this condition. We designed a patient registry to assess the thrombotic risk and features of IVCA. METHODS: In this this multicentre, retrospective, observational study, we included patients with IVCA diagnosed by routine imaging from 20 hospitals in Spain (n=18), Portugal (n=1), and Italy (n=1). Patients were identified from a systematic search in radiology databases using data extraction software (cohort A) and alternative searches in medical records for confirmed IVCA (cohort B; option allowed when systematic approaches were unapplicable). Primary outcomes were clinical and imaging features, thrombotic risk, phenotype of IVCA-associated thrombosis, anticoagulant treatment, and the results of thrombophilia testing. FINDINGS: We included patients with IVCA diagnosed by routine imaging studies done between Jan 1, 2010, and Dec 31, 2022. In the systematic search, 4 341 333 imaging exams were screened from the radiology databases of eight centres. 122 eligible patients were enrolled in cohort A. A further 95 patients were identified by screening medical records at 12 centres, of whom 88 were eligible and included in cohort B, making a combined cohort of 210 patients. 96 (46%) of 210 patients were female and 200 (95%) were European or Hispanic. 60 (29%) of 210 patients had hepatic IVC interruption, whereas 150 (71%) had extrahepatic IVCA. In cohort A, 65 (53%) of 122 patients had venous thrombosis, with an estimated annual risk of 1·15% (95% CI 0·89-1·46). Extrahepatic IVCA was associated with a greater risk of venous thrombosis than hepatic IVCA (56 [67%] of 84 patients vs nine [24%] of 38 patients, odds ratio 5·31, 95% CI 2·27-12·43; p<0·0001). Analysis of 126 patients with venous thrombosis pooled from cohorts A and B showed early-onset (median age 34·6 years, IQR 23·3-54·3) and recurrent events (50 [40%] of 126 patients). Patients with extrahepatic IVCA had greater proportions of lower-limb venous thrombosis (95 [87%] of 109 vs nine [53%] of 17, p=0·0010) and recurrence (48 [44%] of 109 vs two [12%] of 17, p=0·015), but lower rates of pulmonary embolism (10 [10%] of 99 vs four [33%] of 12, p=0·044) than did patients with hepatic IVCA. 77 (63%) of 122 patients with thrombosis underwent indefinite anticoagulation. 32 (29%) of 111 patients (29 [34%] of 86 with thrombosis) had coexisting thrombophilias. The recurrence risk was lower for patients receiving indefinite anticoagulation (adjusted odds ratio 0·24, 95% CI 0·08-0·61; p=0·010), and greater for thrombophilias (3·19, 1·09-9·32; p=0·034). INTERPRETATION: This evaluation of a large patient cohort demonstrates the high thrombotic burden of IVCA. We have identified two distinct forms of IVCA, hepatic and extrahepatic, suggesting different underlying mechanisms. Beyond clinical characterisation, we draw attention to this orphan disease and highlight the need for its study and improved care. FUNDING: Spanish Society of Thrombosis and Haemostasis, Instituto de Salud Carlos III, FEDER, Fundación Séneca.

Thoracoabdominal Aneurysm Repair During Early Stage of Pregnancy: Can and Should We Save the Baby?

Aortic dissection during pregnancy is a life-threatening condition for both mother and fetus. We present the case of a 34-year-old woman with a rapidly expanding abdominal aorta in the context of a chronic type B aortic dissection. A 4 to 6 weeks' viable pregnancy was incidentally diagnosed during the preoperative workup. She underwent urgent extent II thoracoabdominal aortic aneurysm repair with left-sided heart bypass. Postoperatively, vaginal ultrasound evaluation confirmed viability of the fetus, but the patient wished to terminate the pregnancy because of the possible unknown hypoxic effects on the fetus.

Open descending and thoracoabdominal aortic replacement: operative steps for patients with prior endovascular treatment.

Open surgery remains the gold standard for the treatment of the thoracoabdominal aorta. The rising number of endovascularly treated patients comes with an increase in the number of patients who require secondary open interventions due to the complex nature of the aortic disease or to treat endovascular complications. We describe our current approach to secondary open extent II thoracoabdominal aortic repair in patients with prior endovascular repair. In this case report, we show two different cases that exemplify this scenario.

The meningeal transcriptional response to traumatic brain injury and aging.

Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders, however, we still lack fundamental knowledge about meningeal biology. Here, we utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate the transcriptional response of the meninges to traumatic brain injury (TBI) and aging in the sub-acute and chronic time frames. Using single-cell RNA sequencing (scRNA-seq), we first explored how mild TBI affects the cellular and transcriptional landscape in the meninges in young mice at one-week post-injury. Then, using bulk RNA-seq, we assessed the differential long-term outcomes between young and aged mice following TBI. In our scRNA-seq studies, we highlight injury-related changes in differential gene expression seen in major meningeal cell populations including macrophages, fibroblasts, and adaptive immune cells. We found that TBI leads to an upregulation of type I interferon (IFN) signature genes in macrophages and a controlled upregulation of inflammatory-related genes in the fibroblast and adaptive immune cell populations. For reasons that remain poorly understood, even mild injuries in the elderly can lead to cognitive decline and devastating neuropathology. To better understand the differential outcomes between the young and the elderly following brain injury, we performed bulk RNA-seq on young and aged meninges 1.5 months after TBI. Notably, we found that aging alone induced upregulation of meningeal genes involved in antibody production by B cells and type I IFN signaling. Following injury, the meningeal transcriptome had largely returned to its pre-injury signature in young mice. In stark contrast, aged TBI mice still exhibited upregulation of immune-related genes and downregulation of genes involved in extracellular matrix remodeling. Overall, these findings illustrate the dynamic transcriptional response of the meninges to mild head trauma in youth and aging.

Managing the Root in Acute Type A Aortic Dissections: Are We Ready for a Standardized Approach?

OBJECTIVES: Surgical repair of Type A aortic dissection (TAAD) requires exclusion of the primary entry tear and reestablishment of flow into the distal true lumen. Provided that the majority of tears occur within the ascending aorta (AA), replacing only that segment seems a safe option; however, this strategy leaves the root susceptible to dilatation and need for reintervention. We aimed to review the outcomes of the two strategies: aortic root replacement (ARR) and isolated ascending aortic replacement. METHODS: Retrospective analysis of prospectively collected data for all consecutive patients who underwent repair of acute TAAD at our institution from 2015 to 2020 was conducted. Patients were divided into two groups: (1) ARR and (2) isolated AA replacement as index operation for TAAD repair. Primary outcomes were mortality and need for reintervention during the follow-up. RESULTS: A total of 194 patients were included in the study; 68 (35%) in the ARR group and 126 (65%) in the AA group. There were no significant differences in postoperative complications or in-hospital mortality (23%; p = 0.51) between groups. Seven patients (4.7%) died during follow-up and eight patients underwent aortic reinterventions, including proximal aortic segments (two patients) and distal procedures (six patients). CONCLUSION: Both aortic root and AA replacement are acceptable and safe techniques. The growth of an untouched root is slow, and reintervention in this aortic segment is infrequent compared with distal aortic segments, hence preserving the root could be an option for older patients provided that there is no primary tear within the root.

Phagocytosis in the retina promotes local insulin production in the eye.

The retina is highly metabolically active, relying on glucose uptake and aerobic glycolysis. Situated in close contact to photoreceptors, a key function of cells in the retinal pigment epithelium (RPE) is phagocytosis of damaged photoreceptor outer segments (POS). Here we identify RPE as a local source of insulin in the eye that is stimulated by POS phagocytosis. We show that Ins2 messenger RNA and insulin protein are produced by RPE cells and that this production correlates with RPE phagocytosis of POS. Genetic deletion of phagocytic receptors ('loss of function') reduces Ins2, whereas increasing the levels of the phagocytic receptor MerTK ('gain of function') increases Ins2 production in male mice. Contrary to pancreas-derived systemic insulin, RPE-derived local insulin is stimulated during starvation, which also increases RPE phagocytosis. Global or RPE-specific Ins2 gene deletion decreases retinal glucose uptake in starved male mice, dysregulates retinal physiology, causes defects in phototransduction and exacerbates photoreceptor loss in a mouse model of retinitis pigmentosa. Collectively, these data identify RPE cells as a phagocytosis-induced local source of insulin in the retina, with the potential to influence retinal physiology and disease.

An exploratory cost-effectiveness analysis of a novel tissue valve compared with mechanical valves for surgical aortic valve replacement in subgroups of people aged 55-64 and 65+ with aortic stenosis in the UK.

OBJECTIVE: Exploratory analysis to conceptualize and evaluate the potential cost-effectiveness and economic drivers of using a novel tissue valve compared with mechanical heart valves for surgical aortic valve replacement (SAVR) in people aged 55-64 and 65+ with aortic stenosis (AS) from a National Health Service (NHS) UK perspective. METHODS: A decision-analytic model was developed using a partitioned survival model. Parameter inputs were obtained from published literature. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted to explore the uncertainty around the parameters. RESULTS: The novel tissue valve was potentially associated with higher quality-adjusted life years (QALYs) of 0.01 per person. Potential cost savings were greatest for those aged 55-64 (£408) versus those aged 65+(£53). DSA indicated the results to be most dependent on relative differences in general mortality, procedure costs, and reoperation rates. PSA estimated around 75% of the iterations to be cost-effective at £20,000 per QALY for those aged 55-64, and 57% for those aged 65+. CONCLUSIONS: The exploratory analysis suggests that the novel tissue valve could be a cost-effective intervention for people over the age of 55 with AS who are suitable for SAVR in the UK.

Retrograde type A aortic dissection: a different evil.

Retrograde type A aortic dissection (RTAAD) can be spontaneous or secondary to the instrumentation of the descending and thoraco-abdominal aorta. It has anatomical differences compared to antegrade type A aortic dissection that impact the management and prognosis. Treatment is not standardized. We report our approach to spontaneous RTAAD in our institution between 2018 and 2022 (n = 15). The mean age was 60.1 years and 93% were male. Aortic valve, coronary arteries and supra-aortic trunks were spared by the dissection in 80% of the cases; distal extension to iliacs was common and lower limb malperfusion was present in 4 cases (27%). The ascending aorta was dilated at presentation in 60% of the cases. Emergency surgery with arch/FET replacement was offered to 11 patients (73%); 3 patients (20%) received a limited proximal aortic repair; 1 patient was treated conservatively. Overall mortality was 47% (100% for limited proximal repair and 22% for those who received arch/FET). We advocate for aggressive treatment of RTAAD excluding the primary entry tear to prevent immediate- and mid-term complications.

The LINCE Project: A Pathway for Diagnosing NCL2 Disease.

Introduction: Neuronal Ceroid Lipofuscinosis (NCL) comprises a clinically and genetically heterogeneous group of 13 neurodegenerative lysosomal storage disorders. Neuronal Ceroid lipofuscinosis type 2 disease (NCL2), caused by the deficient lysosomal enzyme tripeptidyl peptidase 1 (TPP1), is the only one with an approved enzyme replacement treatment (ERT). Early initiation of ERT appears to modify significantly the natural history of the disease. We aimed to shorten the time to diagnosis of NCL2. Methods: In March 2017, we started per first time in Spain a selective screening program, the LINCE project, in pediatric patients with clinical symptoms compatible with NCL2 disease. The program covered the whole country. We distributed kits to pediatricians with the necessary material to assess patients. All samples in this study were received within one week of collection. Enzymatic activity determined on dried blood spots was the main method used to screen for TPP1 and palmitoyl protein thioesterase 1 (PPT1) for the differential diagnosis with neuronal ceroid lipofuscinosis type 1 (NCL1). Results: Over a period of three years, we received 71 samples. The analysis was minimally invasive, relatively cheap and fast-executing. Three cases identified as a direct result of the selective screening strategy were confirmed by genetic study of NCL2 disease with a median age of 4.5 years. Our screening method has a specificity of 100%, and, with the absence to date of false negatives. We did not detect any NCL1-positive cases. Conclusions: LINCE proved to be a simple, useful, and reliable tool for the diagnosis of NCL2, enabling clinicians to diagnose NCL2 faster. The presence of NCL2-positive cases in our population and availability of treatment may facilitate the inclusion of NCL2 in neonatal screening programs for early diagnosis.

Fulminant Herpes Pneumonia Postaortic Surgery with Known Ankylosing Spondylitis.

Herpes simplex virus (HSV) pneumonitis is rare after cardiac surgery. A 36-year-old gentleman with ankylosing spondylitis underwent emergency surgery for a complex aortic aneurysmal disease. Preoperative treatment of aortitis with antitumor necrosis factor and steroid medication and surgical stress including cardiopulmonary bypass potentially created an immunosuppressive state and reactivation of undiagnosed HSV. Rapid HSV pneumonia ensued, culminating in fulminant organ failure and mortality. HSV pneumonia should be considered postoperatively in patients with severe respiratory distress, especially if immunocompromised.