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BACKGROUND: Compelling evidence has shown cardiac involvement in COVID-19 patients. However, the overall majority of these studies use data obtained during the first wave of the pandemic, while recently differences have been reported in disease course and mortality between first- and second wave COVID-19 patients. The aim of this study was to analyze and compare cardiac pathology between first- and second wave COVID-19 patients.METHODS: Autopsied hearts from first- (n = 15) and second wave (n = 10) COVID-19 patients and from 18 non-COVID-19 control patients were (immuno)histochemically analyzed. CD45+ leukocyte, CD68+ macrophage and CD3+ T lymphocyte infiltration, cardiomyocyte necrosis and microvascular thrombosis were quantified. In addition, the procoagulant factors Tissue Factor (TF), Factor VII (FVII), Factor XII (FXII), the anticoagulant protein Dipeptidyl Peptidase 4 (DPP4) and the advanced glycation end-product N(ε)-Carboxymethyllysine (CML), as markers of microvascular thrombogenicity and dysfunction, were quantified.RESULTS: Cardiac inflammation was significantly decreased in second wave compared to first wave COVID-19 patients, predominantly related to a decrease in infiltrated lymphocytes and the occurrence of lymphocytic myocarditis. This was accompanied by significant decreases in cardiomyocyte injury and microvascular thrombosis. Moreover, microvascular deposits of FVII and CML were significantly lower in second wave compared to first wave COVID-19 patients.CONCLUSIONS: These results show that in our cohort of fatal COVID-19 cases cardiac inflammation, cardiomyocyte injury and microvascular thrombogenicity were markedly decreased in second wave compared to first wave patients. This may reflect advances in COVID-19 treatment related to an increased use of steroids in the second COVID-19 wave.

Background The thoracic lymphadenectomy during an esophagectomy for esophageal cancer includes resection of the thoracic duct (TD) compartment containing the thoracic duct lymph nodes (TDLN). However, the role of TD compartment resection is still a topic of debate since metastatic TDLNs have only been demonstrated in squamous cell carcinomas in Eastern esophageal cancer patients. Therefore, the aim of this study was to assess the presence and metastatic involvement of TDLNs in a Western population, in which adenocarcinoma is the predominant type of esophageal cancer. Methods From July 2017 to May 2020 all consecutive patients undergoing an open or robot-assisted transthoracic esophagectomy with concurrent lymphadenectomy and resection of the TD compartment in the University Medical Center Utrecht, The Netherlands and the Citta della Salute e della Scienza University Hospital in Turin, Italy were included. The TD compartment was resected en bloc and was separated in the operation room by the operating surgeon after which it was macro- and microscopically assessed for (metastatic) TDLNs by the pathologist. Results A total of 117 patients with an adenocarcinoma (73%) or squamous cell carcinoma (27%) of the esophagus were included. In 61 (52%) patients TDLNs were found, containing metastasis in 9 (15%) patients. No major complications related to TD compartment resection were observed. Conclusions This is the first study to demonstrate the presence of metastatic TDLNs in adenocarcinomas of the esophagus. This result provides a valid argument to routinely extend the thoracic lymphadenectomy with resection of the TD compartment during an esophagectomy for esophageal cancer.

Various lymph node functions are regulated by the sympathetic nervous system as shown in rodent studies. If human lymph nodes show a comparable neural regulation, their afferent nerves could represent a potential therapeutic target to treat, for example, infectious or autoimmune disease. Little information is available on human lymph node innervation and the aim of this study is to establish a comprehensive and accurate representation of the presence and location of sympathetic nerves in human lymph nodes. Since previous studies mention sympathetic paravascular nerves to occasionally extent into T cell‐rich regions, the relation of these nerves with T cells was studied as well. A total number of 15 inguinal lymph nodes were resected from six donated human cadavers. Lymph node sections were stained with HE and a double T/B cell staining for evaluation of their morphology and to screen for general pathologies. A triple stain was used to identify blood vessels, sympathetic nerves and T cells, and, to study the presence and location of sympathetic nerves and their relation to T cells. To evaluate whether the observed nerves were en route to other structures or were involved in local processes, adjacent slides were stained with a marker for varicosities (synaptophysin), which presence is suggestive for synaptic activity. All lymph nodes contained sympathetic nerves, both as paravascular and discrete structures. In 15/15 lymph nodes, nerves were observed in their capsule, medulla and hilum, whereas only 13/15 lymph nodes contained nerves in their cortex. The amount of sympathetic nerves varied between compartments and between and within individuals. In general, if a lymph node contained more paravascular nerves in a specific compartment, more discrete nerves were observed as well. Occasionally, discrete nerves were observed in relation to T cells in lymphoid tissues of the cortex and medulla. Furthermore, discrete nerves were frequently present in the capsule and hilum. The presence of varicosities in a portion of these nerves, independently to their compartment, suggested a local regulatory function for these nerves. Human lymph nodes contain sympathetic nerves in their capsule, trabeculae, cortex, medulla and hilum, both as paravascular or as discrete structures. Discrete nerves were observed in relation to T cells and non‐T cell‐rich areas such as the hilar and capsular connective tissue. The presence of discrete structures suggests neural regulation of structures other than blood vessels, which was further supported by the presence of varicosities in a portion of these nerves. These observations are of relevance in further understanding neural regulation of lymph node immune responses and in the development of neuromodulatory immune therapies., Human lymph nodes contain a significant number of sympathetic nerves (black encircled, pink stained TH positive structures). These nerves can be observed surrounding vascular structures, but also as discrete entities in the capsule, cortex, medulla and hilum. In the medulla, these nerves are frequently observed in proximity with immune cells such as T lymphocytes (CD3 positive cells as shown in the right images). Sympathetic nerves in lymph nodes might contribute to neuro immune regulation of lymph node immune function.

Purpose and context. Angiotensin-converting enzyme 2 is the entry receptor for SARS-CoV and SARS-CoV-2. Variations in ACE2 expression might explain age-related symptomatology of COVID-19, that is, more gastro-intestinal symptoms and less pulmonary complaints. This study qualitatively investigated ACE2 protein expression in various organs from the fetal to the young adolescent stage. Method. Autopsy samples from lung, heart, liver, stomach, small intestine, pancreas, kidney, adrenals, and brain (when available) were obtained from twenty subjects aged 24 weeks gestational age through 28 years. Formalin-fixed paraffin-embedded 4-um-thick tissue sections were stained against ACE2. Key results. We showed that the extent of ACE2 expression is age-related. With age, expression increases in lungs and decreases in intestines. In the other examined organs, ACE2 protein expression did not change with age. In brain tissue, ACE2 was expressed in astrocytes and endothelial cells. Conclusions. Age-related ACE2 expression differences could be one substrate of the selective clinical vulnerability of the respiratory and gastro-intestinal system to SARS-CoV-2 infection during infancy.

Background Extra-regional lymph node metastases strongly determine treatment options in patients with esophageal cancer. Staging modalities such as (FDG-PET) CT scanning frequently show activity in retroperitoneal and lung hilar lymph nodes. This study evaluated the incidence of histologically confirmed metastases, treatment approach and recurrence patterns in patients with (FDG-PET) CT positivity in these regions. Methods All patients with (FDG-PET-) CT positive hilar and/or retroperitoneal lymph nodes at primary staging or restaging discussed at a multidisciplinary tumor board meeting for staging of esophageal cancer between January 2012–December 2017 were included. Biopsies and follow-up were evaluated to determine the presence of metastases and progression rates. Results From 2012 to 2017, 65 of 857 patients (7.6%) were selected with positive retroperitoneal and/or hilar lymph nodes. A total of 47/65 (72.3%) patients had positive retroperitoneal lymph nodes, which contained metastases in 19 (29.2%). When no biopsy was performed and curative treatment was given (n = 14), 9 patients had progression or locoregional and distant recurrence. Positive hilar lymph nodes were identified in 21 (32.3%) patients; 4 were biopsied and none contained metastases. In these patients no recurrence of disease was seen during follow-up. Conclusions The majority of biopsied (PET)CT-positive retroperitoneal lymph nodes at staging contained metastases, while biopsied (PET)CT-positive hilar nodes did not. Histological evaluation of (PET)CT -positive retroperitoneal lymph nodes at staging imaging is recommended, while based on this small series, (PET)CT-positive hilar lymph nodes most likely represent reactive lymphadenopathy.

COVID-19 is a pandemic with high morbidity and mortality. In an autopsy cohort of COVID-19 patients, we found extensive accumulation of the tryptophan degradation products 3-hydroxy-anthranilic acid and quinolinic acid in the lungs, heart, and brain. This was not related to the expression of the tryptophan-catabolizing indoleamine 2,3-dioxygenase (IDO)-1, but rather to that of its isoform IDO-2, which otherwise is expressed rarely. Bioavailability of tryptophan is an absolute requirement for proper cell functioning and synthesis of hormones, whereas its degradation products can cause cell death. Markers of apoptosis and severe cellular stress were associated with IDO-2 expression in large areas of lung and heart tissue, whereas affected areas in brain were more restricted. Analyses of tissue, cerebrospinal fluid, and sequential plasma samples indicate early initiation of the kynurenine/aryl-hydrocarbon receptor/IDO-2 axis as a positive feedback loop, potentially leading to severe COVID-19 pathology. © 2021 The Authors. The Journal of Pathology published by John WileySons, Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Background and objective Patients with coronavirus disease 2019 (COVID‐19) pneumonia present with typical findings on chest computed tomography (CT), but the underlying histopathological patterns are unknown. Through direct regional correlation of imaging findings to histopathological patterns, this study aimed to explain typical COVID‐19 CT patterns at tissue level. Methods Eight autopsy cases were prospectively selected of patients with PCR‐proven COVID‐19 pneumonia with varying clinical manifestations and causes of death. All had been subjected to chest CT imaging 24–72 h prior to death. Twenty‐seven lung areas with typical COVID‐19 patterns and two radiologically unaffected pulmonary areas were correlated to histopathological findings in the same lung regions. Results Two dominant radiological patterns were observed: ground‐glass opacity (GGO) (n = 11) and consolidation (n = 16). In seven of 11 sampled areas of GGO, diffuse alveolar damage (DAD) was observed. In four areas of GGO, the histological pattern was vascular damage and thrombosis, with (n = 2) or without DAD (n = 2). DAD was also observed in five of 16 samples derived from areas of radiological consolidation. Seven areas of consolidation were based on a combination of DAD, vascular damage and thrombosis. In four areas of consolidation, bronchopneumonia was found. Unexpectedly, in samples from radiologically unaffected lung parenchyma, evidence was found of vascular damage and thrombosis. Conclusion In COVID‐19, radiological findings of GGO and consolidation are mostly explained by DAD or a combination of DAD and vascular damage plus thrombosis. However, the different typical CT patterns in COVID‐19 are not related to specific histopathological patterns. Microvascular damage and thrombosis are even encountered in the radiologically normal lung., We present direct regional comparison of the most frequently observed pulmonary computed tomography (CT) patterns with corresponding histopathological patterns in an autopsy cohort of eight coronavirus disease 2019 (COVID‐19) patients. While different stages of diffuse alveolar damage are key tissue substrates of the CT patterns in COVID‐19, vascular damage and thrombosis contribute to these typical radiological findings as well. See related Editorial

Milky spots are unique lymphoid structures in the greater omentum that participate in both immune homeostasis of the peritoneal cavity and formation of omental metastases. We developed a rapid and simple staining method to enable macro- or stereomicroscopic identification of these miniscule structures in large samples of fixed human greater omentum. By immersing approximately 6 × 4 cm samples of omental tissue in hematoxylin, these samples could be evaluated quickly for the presence of milky spots. We used an alum hematoxylin variant containing 1 g hematoxylin, 50 g aluminium ammonium sulfate, 0.2 g sodium iodide, 1 g citric acid and 50 g chloral hydrate. This staining method enabled us to determine the number, location, dimensions and topographical relation of milky spots to other structures. Our method also facilitates isolation of milky spots for further investigation. Hematoxylin imparts a blue color to the milky spots, which remains in place during further processing for paraffin embedding. This enabled easy recognition of milky spots during transfer through various solutions and permitted selection of relevant paraffin slides prior to additional staining.

The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global outbreak and prompted an enormous research effort. Still, the subcellular localization of the corona virus in lungs of COVID-19 patients is not well understood. Here, the localization of the SARS-CoV-2 proteins is studied in postmortem lung material of COVID-19 patients and in SARS-CoV-2 infected Vero cells, processed identically. Correlative light and electron microscopy on semi-thick cryo-sections, demonstrated induction of electron-lucent, lipid filled compartments after SARS-CoV-2 infection in both lung and cell cultures. In infected Vero cells and using immuno-electron microscopy, viral proteins were detected in these lipid filled compartments. In addition, several viral proteins were detected in virus particles, Golgi, double membrane spherules and multiple-virus bodies which were not lysosomal. In lung tissue, the non-structural protein 4 and the stable nucleocapsid N-protein, were detected on membranes of lipid filled compartments. The induction of such lipid filled compartments and the localisation of the viral proteins in lung of patients with fatal COVID-19, may explain the extensive inflammatory response. Authors Summary The trafficking of coronaviruses in lung of COVID-19 patients is not well understood and virus particles are difficult to find. Here we have visualized virus particles in SARS-CoV-2 infected cells by focusing on viral protein detection, in combination with ultrastructure. We studied how the virus is altering the cell morphology and determined that in Vero cells, lipid filled compartments contained various viral proteins. In these cells, also membrane enclosed multi-virus bodies were visible that contain a different set of viral proteins. We demonstrated that lipid filled compartments are viral induced compartments, as no known cellular marker such as lipid droplet or lysosomal marker was present. Using this knowledge, we then studied lung tissue from patients with a fatal SARS-Cov-2 infection, processed in a similar manner. Again we detected lipid filled compartments, now with viral proteins nsp4 and the stable nucleocapsid N-protein. The presence of these lipid filled compartments with viral proteins induced by SARS-CoV-2 infections, could be why the immune response of the COVID-19 patients is so strong, resulting in a fatal infection, and should be considered for new therapeutic strategies.

SARS-CoV-2 may cause acute respiratory disease, but the infection can also initiate neurological symptoms. Here we show that SARS-CoV-2 infection causes brain inflammation in the macaque model. An increased metabolic activity in the pituitary gland of two macaques was observed by longitudinal positron emission tomography-computed tomography (PET-CT). Post-mortem analysis demonstrated infiltration of T-cells and activated microglia in the brain, and viral RNA was detected in brain tissues from one animal. We observed Lewy bodies in brains of all rhesus macaques. These data emphasize the virus’ capability to induce neuropathology in this nonhuman primate model for SARS-CoV-2 infection. As in humans, Lewy body formation is an indication for the development of Parkinson’s disease, this data represents a warning for potential long-term neurological effects after SARS-CoV-2 infection.TeaserSARS-CoV-2 causes brain inflammation and Lewy bodies, a hallmark for Parkinson, after an asymptomatic infection in macaques.

Summary: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy. Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response. The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy. Methods: This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands. With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020. In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course. Findings: Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41–78). Median disease course (time from onset of symptoms to death) was 22 days (range 5–44 days). In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course. Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract. In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain. In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata. Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5–44]; ten patients with neutrophilic plugs, 21 days [5–44]). Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets.. Interpretation: In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs. However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19. This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19. Funding: Amsterdam UMC Corona Research Fund.

Omental milky spots (OMSs) are the primary lymphoid structures of the greater omentum. However, the presence of lymph nodes (LNs) has occasionally been mentioned as well. Understanding which lymphoid structures are present is of significance, especially in gastric tumor metastasis; tumor deposits in omental LNs suggest local lymphatic spread, whereas tumor deposits in OMSs suggest peritoneal spread and hence extensive disease. Since LNs and OMSs share morphological characteristics and OMSs might be wrongly identified as LNs, reliable hallmarks facilitating easy discrimination are needed.A series of microscopic morphological hallmarks unique to LNs were selected as potential candidates and were assessed for their discriminative capacity: 1) capsule, 2) trabeculae, 3) subcapsular sinus, 4) afferent lymphatic vessels, 5) distinct B- and T cell regions, and 6) a layered organization with, from the outside in a capsule, cortex, paracortex, and medulla. These hallmarks were visualized by multiple staining techniques.Hallmarks 1, 2 5 and 6 were shown to be the most efficient as these were consistent and discriminative. They were best visualized by Picrosirius red, smooth muscle actin and a B-cell / T-cell double staining.The presence of a capsule, trabeculae, distinct B- and T-cell regions and a layered organization represent consistent and reliable morphological features which allow to easily distinguish LNs from OMSs, especially when applied in combination.

Background Resection of the thoracic duct is part of the formal en bloc mediastinal esophagolymphadenectomy for cancer, although with the adaptation of minimally invasive techniques, some centers started to leave the thoracic duct compartment in situ. However, previous studies reported thoracic duct lymph nodes in this compartment that may contain metastasis. The aim of this study was to assess the presence and number of lymph nodes in the fatty tissue surrounding the thoracic duct. Methods A right-sided thoracoscopic esophagectomy was performed on seven fresh-frozen human cadavers (male, n = 3; female, n = 4). The esophagus and lymph node stations 7, 8, and 9 were resected en bloc, followed by resection of the thoracic duct compartment consisting of the fatty tissue covering the aorta, the thoracic duct and thoracic duct lymph nodes. Lymph nodes were visualized by a hematoxylin and eosin stain and counted macroscopically and microscopically. Results Thoracic duct lymph nodes were found in 6 of 7 cadavers (86%), with a median number of 1 (range, 0 to 6). Nodes were predominantly located in the area of the azygos vein. A median of 4 subcarinal nodes (range, 1 to 8) and 2 periesophageal nodes (range, 1 to 4) were present. Conclusions This study shows that thoracic duct lymph nodes are located within the fatty tissue surrounding the thoracic duct. Resection of this compartment during an esophagectomy for cancer increases lymph node yield.

Omental milky spots (OMSs), small lymphoid structures positioned in the greater omentum, are involved in peritoneal immune homeostasis and the formation of omental metastases. Sympathetic nerve activity is known to regulate immune function in other lymphoid organs (e.g. spleen and lymph nodes) and to create a favourable microenvironment for various tumour types. However, it is still unknown whether OMSs receive sympathetic innervation. Therefore, the aim of this study was to establish whether OMSs of the adult human greater omentum receive sympathetic innervation. A total of 18 OMSs were isolated from five omenta, which were removed from 3% formaldehyde‐perfused cadavers (with a median age of 84 years, ranging from 64 to 94). OMSs were embedded in paraffin, cut and stained with a general (PGP9.5) and sympathetic nerve marker (TH and DBH), and evaluated by bright field microscopy. A T‐cell, B‐cell, and macrophage staining was performed to confirm OMS identity. In 50% of the studied OMSs, sympathetic nerve fibres were observed at multiple levels of the same OMS. Nerve fibres were represented as dots or elongated structures and often observed in relation to small vessels and occasionally as individual structures residing between lymphoid cells. The current study shows that 50% of the investigated OMSs contain sympathetic nerve fibres. These findings may contribute to our understanding of neural regulation of peritoneal immune response and the involvement of OMSs in omental metastases., This study shows that human omental milky spots (OMSs) contain sympathetic nerve fibres. Often, these nerve fibres were located around small blood vessels and occasionally individual nerve fibres were observed between lymphoid cells. The presence of sympathetic fibres in OMSs contributes to our understanding of how OMS immune function might be regulated during an abdominal immune challenge and why they form primary implantation sites for peritoneal exfoliated cancer cells.

Background Chylothorax is a treacherous complication after esophagectomy associated with significant morbidity. Early enteral nutrition after esophagectomy is important for recovery but increases the pressure in the lymphatic system owing to the absorption of triglycerides. To lower the incidence of chylothorax after esophagectomy, the use of low fat–containing tube feeding was evaluated as a standard of care after esophagectomy. Methods All consecutive patients who underwent an esophagectomy with gastric tube reconstruction and placement of jejunostomy at the University Medical Center Utrecht between January 1, 2012, and December 31, 2017, were included. Tube feeding was started as standard of care on postoperative day 1 with a normal fat–containing formula in the period between 2012 and 2014 and with a low fat–containing formula between 2014 and 2017. Results Between 2012 and 2017, 198 patients were included. The tube feeding formula contained normal fat in 86 (43.4%) and low fat in 112 (53.6%). Chylothorax, associated with triglyceride levels exceeding 1.24 mmol/L in 27 patients (61.4%) with a clinical diagnosis of chylothorax, was significantly less observed in the low fat–formula group (15 [13.4%] vs 29 [33%], p = 0.001). No difference was seen in drain output, triglyceride levels in the pleura fluid, treatment strategy, and hospital mortality. At multivariable analysis, the normal-fat formula was associated with a 5.1 odds (95% confidence interval, 2.1 to 12.1) for postoperative chylothorax. Other factors independently associated with chylothorax were transthoracic resection, anastomotic leakage, number of resected lymph nodes, and lower body mass index. Conclusions Administration of low fat–containing tube feed after esophagectomy was associated with a lower incidence of chylothorax.

Introduction A subset of oesophageal cancer patients has residual nodal disease despite complete pathologic response of the primary tumour after neoadjuvant chemoradiation and resection. The aim of this study was to determine the exact location of metastatic nodes with regard to the neoadjuvant radiation field and to assess progression-free (PFS) and overall survival (OS) in this group of patients. Materials and methods From January 2010 to January 2017, complete tumour responders (ypT0) after neoadjuvant chemoradiotherapy and oesophagectomy were identified from a prospective database and grouped according to residual nodal disease (ypT0N + or ypT0N0). Radiation fields were analysed for location of the metastatic nodes and PFS and OS were determined. Results In a total of 192 patients, 53 complete responders (ypT0) were identified. Of those, 11 patients (20.8%) were ypT0N+ with a total of 12 metastatic nodes: 8 (66.7%) located within the neoadjuvant radiation field and 4 (33.3%) located outside this field. Although not statistically significant, 1- and 2-year PFS were worse in ypT0N + patients (ypT0N+ 64.3% vs. ypT0N0 84.4%; ypT0N+ 48.2% vs. ypT0N0 80.7%, respectively; p = 0.051), just as 1- and 2-year OS rates, however, to a lesser extent (ypT0N+ 75.0% vs. ypT0N0 76.3%; ypT0N+ 75.0% vs. ypT0N0 72.9%, respectively; p = 0.956). Conclusion Most ypT0N + lymph nodes are located within the neoadjuvant radiation field. Although a small heterogeneous population was included, this might be due to an inadequate response to neoadjuvant chemoradiotherapy leading to a trend towards worse PFS and OS in ypT0N + patients. Larger studies need to validate our findings.

Background General anesthesia during infancy is associated with neurocognitive abnormalities. Potential mechanisms include anesthetic neurotoxicity, surgical disease, and cerebral hypoxia–ischemia. This study aimed to determine the incidence of low cerebral oxygenation and associated factors during general anesthesia in infants. Methods This multicenter study enrolled 453 infants aged less than 6 months having general anesthesia for 30 min or more. Regional cerebral oxygenation was measured by near-infrared spectroscopy. We defined events (more than 3 min) for low cerebral oxygenation as mild (60 to 69% or 11 to 20% below baseline), moderate (50 to 59% or 21 to 30% below baseline), or severe (less than 50% or more than 30% below baseline); for low mean arterial pressure as mild (36 to 45 mmHg), moderate (26 to 35 mmHg), or severe (less than 25 mmHg); and low pulse oximetry saturation as mild (80 to 89%), moderate (70 to 79%), or severe (less than 70%). Results The incidences of mild, moderate, and severe low cerebral oxygenation were 43%, 11%, and 2%, respectively; mild, moderate, and severe low mean arterial pressure were 62%, 36%, and 13%, respectively; and mild, moderate, and severe low arterial saturation were 15%, 4%, and 2%, respectively. Severe low oxygen saturation measured by pulse oximetry was associated with mild and moderate cerebral desaturation; American Society of Anesthesiology Physical Status III or IV versus I was associated with moderate cerebral desaturation. Severe low cerebral saturation events were too infrequent to analyze. Conclusions Mild and moderate low cerebral saturation occurred frequently, whereas severe low cerebral saturation was uncommon. Low mean arterial pressure was common and not well associated with low cerebral saturation. Unrecognized severe desaturation lasting 3 min or longer in infants seems unlikely to explain the subsequent development of neurocognitive abnormalities.

Contains fulltext : 136013.pdf (Publisher’s version ) (Closed access) BACKGROUND: Gastrointestinal symptoms are frequently reported adverse effects of antidepressants, but antidepressants are also a treatment modality in functional gastrointestinal disorders. We aimed to assess the association between antidepressant use and gastrointestinal symptoms in the general adult population. METHODS: We assessed gastrointestinal symptoms, medication use, and comorbidity through structured questionnaires in randomly selected individuals. We compared presence of gastrointestinal symptoms in respondents who reported antidepressant use with those who did not. We used multivariable regression analysis to verify the association between antidepressant use and gastrointestinal symptoms. RESULTS: In total, 16,758 questionnaires were returned and eligible for analysis. Antidepressant use was reported by 701 respondents (4.2%). Gastrointestinal symptoms were more frequently reported by antidepressant users compared with nonusers (40% vs 25%, P < 0.01). This apparent association between antidepressant use and gastrointestinal symptoms did not remain after adjusting for demographic factors, comorbidity, and use of other medications (adjusted odds ratio, 0.94; 95% confidence interval, 0.74-1.18). CONCLUSIONS: In our cross-sectional population-based study, we did not find an association between antidepressant use and gastrointestinal symptoms.

PURPOSE: To describe and discuss the diagnostic and treatment complexity of lymphatic system complications after scoliosis surgery. METHODS: Surgery for adolescent idiopathic scoliosis is very commonly performed with posterior pedicle screw instrumentation. Complications of the anteriorly based lymphatic system are, therefore, rare. We present a case with complications related to the lymphatic system, which have not been reported before after this type of surgery. RESULTS: After standard Th3 to Th12 posterior spinal reduction and fusion of a moderate thoracic curve, chyluria and a chylothorax developed in an adolescent girl. This appeared to be caused by an obstruction of the thoracic duct. Thorax drainage and finally thoracoscopic intervention prevented further pulmonal impairment. The exact cause could not be identified and the persistent lymph drainage problems had to be treated with a medium chain triglyceride diet. CONCLUSION: With this report, we aim to create awareness of the lymphatic system in general and the possibility of severe complications, even after a posterior only approach of the vertebral column.

Background Chylothorax is a treacherous complication after esophagectomy associated with significant morbidity. Early enteral nutrition after surgery is important for recovery, but increases the pressure in the lymphatic system due to the absorption of triglycerids. To lower the incidence of chylothorax after esophagectomy, the use of low fat-containing tube feeding was evaluated as a standard of care following esophagectomy. Methods All consecutive patients who underwent an esophagectomy with gastric tube reconstruction and placement of jejunostomy at the UMC Utrecht between the 1st of January 2012 and the 31st of December 2017 were included. Tube feeding was started as standard of care on postoperative day 1 with a normal fat-containing formula in the period between 2012 and 2014 and with a low fat-containing formula between 2014 and 2017. The clinical diagnosis of chylothorax was confirmed by triglyceride levels > 1.24mmol/L in 27 patients (61.4%). Results Between 2012–2017 200 patients were included; 88(44.0%) received normal fat-containing tube feeding, 112(56.0%) low fat-containing tube feeding. Chylothorax was significantly less observed in the low fat formula group (n = 15, 13.4% versus n = 29, 33%, P = 0.001) No difference was seen in drain output, triglyceride levels in the pleura fluid, treatment strategy and hospital mortality. At multivariable analysis normal fat formula was associated with a 5.1 [2.1–12.1] odds for postoperative chylothorax. Other factors independently associated with chylothorax were transthoracic resection, anastomotic leakage, number of resected lymph nodes, and lower body mass index. Conclusion Administration of low fat-containing tube feed after esophagectomy lowers the incidence of chylothorax. Disclosure All authors have declared no conflicts of interest.

Background Injury and subsequent leakage of unrecognized thoracic duct tributaries during transthoracic esophagectomy may lead to chylothorax. Therefore, we hypothesized that thoracic duct anatomy at the diaphragm is more complex than currently recognized and aimed to provide a detailed description of the anatomy of the thoracic duct at the diaphragm. Basic procedures The thoracic duct and its tributaries were dissected in 7 (2 male and 5 female) embalmed human cadavers. The level of origin of the thoracic duct and the points where tributaries entered the thoracic duct were measured using landmarks easily identified during surgery: the aortic and esophageal hiatus and the arch of the azygos vein. Main findings The thoracic duct was formed in the thoracic cavity by the union of multiple abdominal tributaries in 6 cadavers. In 3 cadavers partially duplicated systems were present that communicated with interductal branches. The thoracic duct was formed by a median of 3 (IQR: 3–5) abdominal tributaries merging 8.3 cm (IQR: 7.3–9.3 cm) above the aortic hiatus, 1.8 cm (IQR: −0.4 to 2.4 cm) above the esophageal hiatus, and 12.3 cm (IQR: 14.0 to −11.0 cm) below the arch of the azygos vein. Conclusion This study challenges the paradigm that abdominal lymphatics join in the abdomen to pass the diaphragm as a single thoracic duct. In this study, this occurred in 1/7 cadavers. Although small, the results of this series suggest that the formation of the thoracic duct above the diaphragm is more common than previously thought. This knowledge may be vital to prevent and treat post-operative chyle leakage.