Anatomic patterns of anastomotic leaks after Ivor Lewis esophagectomy for cancer: Impact on management and outcomes.

BACKGROUND: Anastomotic leakage presentation after Ivor Lewis esophagectomy may vary on imaging. Such variations may influence anastomotic leakage management and outcomes. METHODS: All consecutive patients who underwent Ivor Lewis esophagectomy for cancer between 2012 and 2019 in 2 referral centers were included. Anatomical patterns of anastomotic leakage were defined on imaging as follows: eso-mediastinal anastomotic leakage was a leak contained in the posterior mediastinum, eso-pleural anastomotic leakage was a leak involving the pleural cavity, and eso-bronchial anastomotic leakage was a leak communicating with the tracheobronchial tract. According to the Esophageal Complications Consensus Group definition, management and 90-day mortality were evaluated according to these patterns. RESULTS: Among 731 patients, 111 (15%) developed anastomotic leakage consisting of eso-mediastinal anastomotic leakage (n = 87, 79%), eso-pleural anastomotic leakage (n = 16, 14%) and eso-bronchial anastomotic leakage (n = 8, 7%). There was no difference among these groups regarding preoperative characteristics or time to anastomotic leakage diagnosis. There was a significant difference in initial management according to anastomotic leakage anatomic patterns (P = .001). More than half of patients who experienced eso-mediastinal anastomotic leakage (n = 46, 53%) were initially treated conservatively without requiring intervention (Esophageal Complications Consensus Group type I), whereas most patients with eso-pleural anastomotic leakage (n = 14, 87.5%) and all with eso-bronchial anastomotic leakage (n = 8, 100%) initially required interventional or surgical treatment (Esophageal Complications Consensus Group type II-III). Anastomotic leakage anatomic patterns had a statistically significant impact on 90-day mortality, intensive care unit stay, and total hospital stay (P < .001). CONCLUSION: Anastomotic leakage anatomic patterns after Ivor Lewis esophagectomy influence outcomes. Further studies are warranted to validate it in a prospective setting. Anastomotic leakage anatomic patterns may help in guiding anastomotic leakage management.

EGR4 is critical for cell-fate determination and phenotypic maintenance of geniculate ganglion neurons underlying sweet and umami taste.

The sense of taste starts with activation of receptor cells in taste buds by chemical stimuli which then communicate this signal via innervating oral sensory neurons to the CNS. The cell bodies of oral sensory neurons reside in the geniculate ganglion (GG) and nodose/petrosal/jugular ganglion. The geniculate ganglion contains two main neuronal populations: BRN3A+ somatosensory neurons that innervate the pinna and PHOX2B+ sensory neurons that innervate the oral cavity. While much is known about the different taste bud cell subtypes, considerably less is known about the molecular identities of PHOX2B+ sensory subpopulations. In the GG, as many as 12 different subpopulations have been predicted from electrophysiological studies, while transcriptional identities exist for only 3 to 6. Importantly, the cell fate pathways that diversify PHOX2B+ oral sensory neurons into these subpopulations are unknown. The transcription factor EGR4 was identified as being highly expressed in GG neurons. EGR4 deletion causes GG oral sensory neurons to lose their expression of PHOX2B and other oral sensory genes and up-regulate BRN3A. This is followed by a loss of chemosensory innervation of taste buds, a loss of type II taste cells responsive to bitter, sweet, and umami stimuli, and a concomitant increase in type I glial-like taste bud cells. These deficits culminate in a loss of nerve responses to sweet and umami taste qualities. Taken together, we identify a critical role of EGR4 in cell fate specification and maintenance of subpopulations of GG neurons, which in turn maintain the appropriate sweet and umami taste receptor cells.

Introducing N-Heterocyclic Iminophosphoranes (NHIPs): Synthesis by [3 + 2] Cycloaddition of Azophosphines with Alkynes and Reactivity Studies.

Azophosphines (Ar-N═N-PR2) were prepared from N-aryl-N'-(trimethylsilyl)diazenes (Ar-N═N-SiMe3) and R2PCl by Me3SiCl elimination or oxidation of phosphinohydrazines (Ar-NH-NH-PR2) by 2,5-dialkyl-1,4-benzoquinones. Azophosphines underwent 1,3-dipolar cycloaddition with cyclooctyne and dimethylacetylene dicarboxylate to give N-heterocyclic iminophosphoranes (NHIPs), which are structurally similar to cyclic (alkyl)(amino)carbenes. The cycloaddition reaction is compatible with various phosphorus atom substituents including phenyl (NHIP-1,4,6), isopropyl (NHIP-2), cyclohexyl (NHIP-3), and dimethylamino (NHIP-5) groups. The pKBH+ values of the NHIPs in acetonitrile range from 13.13 to 23.14. On the basis of the Huynh electronic parameter, NHIP-1 and NHIP-2 have σ-donor strengths comparable with that of 1,8-diazabicyclo[5.4.0]undec-7-ene. NHIP-1 underwent facile 1,2-addition with pentafluoropyridine to form a rare fluorophosphorane. The treatment of NHIP-1 with triphenylsilane resulted in P-N bond cleavage, accompanied by the reduction of phosphorus(V) to phosphorus(III). A homoleptic, cationic CuI-NHIP-1 complex was also prepared. The potential utility of π-donating NHIPs was demonstrated by the stabilization of a reactive iminoborane (Cl-B≡N-SiMe3). The facile scalable synthesis, tunability of steric demands, and basicity of NHIPs suggest that this new heterocycle class may find a wide range of applications in synthetic chemistry.

Taming phosphorus mononitride.

Phosphorus mononitride (PN) only has a fleeting existence on Earth, and molecular precursors for the release of this molecule under mild conditions in solution have remained elusive. Here we report the synthesis of an anthracene-based precursor-an anthracene moiety featuring an azidophosphine bridge across its central ring-that dissociates into dinitrogen, anthracene and P≡N in solution with a first-order half-life of roughly 30 min at room temperature. Heated under reduced pressure, this azidophosphine-anthracene precursor decomposes in an explosive fashion at around 42 °C, as demonstrated in a molecular-beam mass spectrometry study. The precursor is also shown to serve as a PN transfer reagent in the synthesis of an Fe-NP coordination complex, through ligand exchange with its Fe-N2 counterpart. The terminal N-bonded complex was found to be energetically preferred, compared to its P-bonded linkage isomer, owing to a significant covalent Fe-pnictogen bond character and an associated less unfavourable Pauli repulsion in the metal-ligand interaction.

Reactions of Tri-tert-Butylphosphatetrahedrane as a Spring-Loaded Phosphinidene Synthon Featuring Nickel-Catalyzed Transfer to Unactivated Alkenes.

Cage-opening reactions of the highly strained tri-tert-butylphosphatetrahedrane (1), shown here to function as a synthon of (tri-tert-butylcyclopropenyl)phosphinidene, are described. Treatment of 1 with a base-stabilized silylene led to the corresponding phosphasilene, which was isolated in 72% yield as a red crystalline solid. Phosphinidene transfer was also observed when 1 (2 equiv) was combined with the Wittig reagent Ph3PCH2 to form a diphosphirane (50% isolated yield). The reaction is proposed to proceed through a generated phosphaalkene intermediate, which was characterized by NMR spectroscopy. In addition, we report on nickel-catalyzed phosphinidene transfer to styrene, ethylene, neohexene, and 1,3-cyclohexadiene; the corresponding phosphiranes were isolated in 51-64% yield. Computational studies suggest the intermediacy of a nickel phosphinidene species. Treatment of the ethylene-derived phosphirane product with triflic acid delivered elimination of [tBu3C3]OTf and formation of a P-H bond, illustrating the ability of the tri-tert-butyl cyclopropenyl group to serve as a protecting group that is removable following phosphinidene transfer.

Staudinger Reactivity and Click Chemistry of Anthracene (A)-Based Azidophosphine N3PA.

11-Azido-9,10-dihydro-9,10-phosphanoanthracene (N3PA) has been demonstrated recently as a transfer reagent for molecular phosphorus mononitride (PN) because it easily dissociates at room temperature into dinitrogen (N2), PN, and anthracene (A). Here we report further reactivity studies of the N3PA molecule including strain-promoted 1,3-dipolar cycloaddition with cyclooctyne and Staudinger-type reactivity. Calculations at the DLPNO-CCSD(T)/cc-pVTZ//PBE0-D3(BJ)/cc-pVTZ level of theory indicate that the click reaction is faster than the dissociation of N3PA. The Staudinger-type reactivity enabled transfer of the NPA fragment to a base-stabilized silylene. The previously reported intermediate of vanadium trisanilide with an NPA ligand could be isolated in 61% yield and structurally characterized in a single-crystal X-ray diffraction experiment. In line with the previously reported phosphinidene reactivity of the transient vanadium phosphorus mononitride complex, thermolysis or irradiation of the complex leads to A elimination and formation of the corresponding vanadium PN dimer or trimer, respectively.

Probabilistic public health risks associated with pesticides and heavy metal exposure through consumption of common dried fish in coastal regions of Bangladesh.

The chemical contaminants in dried fish are of great food safety concern and an emerging public health issue in Bangladesh. The aim of this study was to assess the public health risk associated with exposure to pesticides (organochlorine and organophosphorus) and heavy metals (lead, mercury, cadmium, chromium, arsenic) through the consumption of dried fish (Bombay duck, ribbon fish, silver jewfish, shrimp, Chinese promfret) in coastal districts (Cox's Bazar, Chittagong, Bhola, Patuakhali, Khulna) of Bangladesh. Dried fish consumption data were collected from 500 adult respondents (100 from each district) using a food frequency questionnaire (FFQ). Pesticide residues were determined using QuEChERS extraction coupled to gas chromatography and gas chromatography mass spectrometry, and heavy metals were estimated using an atomic absorption spectrophotometric method. The results revealed that the frequency and amount of dried fish consumption was highest for Bombay duck in Cox's Bazar (11.57 g/capita/day) and ribbon fish (12.10 g/capita/day) in Chittagong. The estimated daily intake (EDI, 7.40 × 10-5 to 1.10 × 10-4 mg/kg/day) and health risk index (HRI, 0.013 to 0.16) values expressed no health risk from pesticide residues in all the positive samples. For heavy metals, target hazard quotients (THQ) for non-carcinogenic health risk were below 1 (0.001-0.154), indicating no health risk for all samples. However, carcinogenic risk R value indicated a potential health risk for chromium (2.64 × 10-6 to 4.06 × 10-6), and carcinogenic RT value (2.82 × 10-6 to 5.71 × 10-6) indicated a potential health risk for all the metals. It is concluded that the risk of exposure to pesticides through the consumption of dried fish is low, while heavy metals pose moderate-to-high health risks to dried fish consumers in the study area. Thus, the study suggests an appropriate risk management policy that controls pesticides and heavy metals in dried fish to ensure safe food for local and global consumers, underpinned by a producers' capacity building and consumers' awareness raising strategy.

Proximal tibial dimensions in a formalin-fixed neonatal cadaver sample: an intraosseous infusion approach.

PURPOSE: Methods to administer intramedullary medication and fluid infusion in both adults and children date to the early twentieth century. Studies have shown that intraosseous access in the proximal tibia is ideal for resuscitation efforts as fewer critical structures are at risk, and neither is the blood flow to the lower limbs compromised. Insertion of a needle in children younger than 5 years does have the risk to damage to the epiphyseal growth plate. Therefore, the aim of this study was to determine the ideal intraosseous insertion site distal to the epiphyseal growth plate in neonates. METHODS: The samples consisted of both the left and right sides of 15 formalin-fixed neonatal cadavers. The dimensions were measured on the superior surfaces of each section, anteromedial border, cortical thickness, and medullary space. RESULTS: The most desirable location to gain vascular access is at 10 mm inferior to the tibial tuberosity. CONCLUSION: The smallest cortical thickness (1.32 mm), the largest medullary space (4.50 mm), and the largest anteromedial surface (7.72 mm) were observed at 10 mm inferior to the tibial tuberosity. It is imperative that health care professionals are familiar with the osteological sites that could be safely used for an intraosseous infusion procedure.

Comparative quality assessment of traditional vs. improved dried Bombay duck (Harpodon nehereus) under different storage conditions: Solar chimney dryer a low-cost improved approach for nutritional dried fish.

Dried fish and fishery products provide important and affordable dietary sources of animal protein. The present study compared the sensory, microbial, and biochemical quality of bombay duck (Harpadon nehereous) dried fish produced using improved versus traditional open-air drying method. The sensory, microbial, and biochemical quality was determined following quality index, total plate count (TPC), and Association of Official Analytical Chemists (AOAC) method, respectively. The sensory quality results indicate highly acceptable dried fish with the improved method compared to traditional method at both initial and storage condition. The microbial load (APC, TEC, TViC, and TSC) of improved dried fish was within internationally permissible microbiological standards for food whereas traditionally dried fish exceeded the permissible limit. The biochemical composition (protein, lipid, ash, and moisture) of improved dried fish had better nutritional value than the traditional dried fish. After 60 days storage time, samples packaged under HDPE conditions exhibited excellent organoleptic characteristics, lower microbial load, and lower biochemical decomposition than samples packaged in LDPE. The above results confirmed that the solar chimney dryer produced superior quality of dried fish compared to the traditional open-air drying method both initially and after storage, while packaging dried fish under HDPE conditions extended shelf life further.

Frustrated Lewis Pair Stabilized Phosphoryl Nitride (NPO), a Monophosphorus Analogue of Nitrous Oxide (N2O).

Phosphoryl nitride (NPO) is a highly reactive intermediate, and its chemistry has only been explored under matrix isolation conditions so far. Here we report the synthesis of an anthracene (A) and phosphoryl azide based molecule (N3P(O)A) that acts as a molecular synthon of NPO. Experimentally, N3P(O)A dissociates thermally with a first-order kinetic half-life that is associated with an activation enthalpy of ΔH⧧ = 27.5 ± 0.3 kcal mol-1 and an activation entropy of ΔS⧧ = 10.6 ± 0.3 cal mol-1 K-1 that are in good agreement with calculated DLPNO-CCSD(T)/cc-pVTZ//PBE0-D3(BJ)/cc-pVTZ energies. In solution N3P(O)A undergoes Staudinger reactivity with tricyclohexylphosphine (PCy3) and subsequent complexation with tris(pentafluorophenyl)borane (B(C6F5)3, BCF) to form Cy3P-NP(A)O-B(C6F5)3. Anthracene is cleaved off photochemically to form the frustrated Lewis pair (FLP) stabilized NPO complex Cy3P⊕-N═P-O-B⊖(C6F5)3. An intrinsic bond orbital (IBO) analysis suggests that the adduct is zwitterionic, with a positive and negative charge localized on the complexing Cy3P and BCF, respectively.

Alleviating Strain in Organic Molecules by Incorporation of Phosphorus: Synthesis of Triphosphatetrahedrane.

Phosphatetrahedranes (tBuCP)2 and (tBuC)3P were recently reported and represent the first tetrahedranes containing a mixed carbon/phosphorus core. Herein, we report that tetrahydrofuran (THF) solutions of the parent triphosphatetrahedrane HCP3 may be generated in 31% yield (NMR internal standard yield) by combining [Na(THF)3][P3Nb(ODipp)3] (Dipp = 2,6-diisopropylphenyl), INb(ODipp)3(THF), and bromodichloromethane in thawing THF. While HCP3 was found to be stable in dilute THF solutions for extended periods of time, the concentration of the solution at -40 °C led to the formation of a black precipitate, which has been tentatively assigned as a polymerized form of HCP3. HCP3 reacts readily with (dppe)Fe(Cp*)Cl (dppe = 1,2-bis(diphenylphosphino)ethane, Cp*= η5-C5Me5) in the presence of Na[BPh4] to form a purple cationic iron complex of triphosphatetrahedrane (50% yield), which was structurally characterized in a single-crystal X-ray diffraction experiment. Additionally, we present a series of homodesmotic equations analyzed via quantum chemical calculations that suggest triphosphatetrahedrane is the least strained of the mixed C/P phosphatetrahedranes.

Incidence and Risk Factors for Diaphragmatic Herniation Following Esophagectomy for Cancer.

OBJECTIVE: To evaluate the incidence and risk factors of diaphragmatic herniation following esophagectomy for cancer (DHEC), and assess the results of surgical repair. SUMMARY BACKGROUND DATA: The current incidence of DHEC is discussed with conflicting data regarding its treatment and natural course. METHODS: Monocentric retrospective cohort study (2009-2018). From 902 patients, 719 patients with a complete follow-up of CT scans after transthoracic esophagectomy for cancer were reexamined to identify the occurrence of a DHEC. The incidence of DHEC was estimated using Kalbfleisch and Prentice method and risk factors of DHEC were studied using the Fine and Gray competitive risk regression model by treating death as a competing event. Survival was analyzed. RESULTS: Five-year DHEC incidence was 10.3% [95% CI, 7.8%-13.2%] (n = 59), asymptomatic in 54.2% of cases. In the multivariable analysis, the risk factors for DHEC were: presence of hiatal hernia on preoperative CT scan (HR = 1.72 [1.01-2.94], P = 0.046), previous hiatus surgery (HR = 3.68 [1.61-8.45], P = 0.002), gastroesophageal junction tumor location (HR = 3.51 [1.91-6.45], P < 0.001), neoadjuvant chemoradiotherapy (HR = 4.27 [1.70-10.76], P < 0.001), and minimally invasive abdominal phase (HR = 2.98 [1.60-5.55], P < 0.001). A cure for DHEC was achieved in 55.9%. The postoperative mortality rate was nil, the overall morbidity rate was 12.1%, and the DHEC recurrence rate was 30.3%. Occurrence of DHEC was significantly associated with a lower hazard rate of death in a time-varying Cox's regression analysis (HR = 0.43[0.23-0.81], P = 0.010). CONCLUSIONS: The 5-year incidence of DHEC is 10.3% and is associated with a favorable prognosis. Surgical repair of symptomatic or progressive DHEC is associated with an acceptable morbidity. However, the optimal surgical repair technique remains to be determined in view of the large number of recurrences.

Dimerization and Cycloaddition Reactions of Transient Tri-tert-butylphosphacyclobutadiene Generated by Lewis Acid Induced Isomerization of Tri-tert-butylphosphatetrahedrane.

Tri-tert-butylphosphatetrahedrane (1) is shown here to act as a synthon of isomeric tri-tert-butylphosphacyclobutadiene in the presence of a Lewis acid or transition-metal complex. When it is combined with a substoichiometric amount of triphenylborane, compound 1 forms a ladderane-type dimer of tri-tert-butylphosphacyclobutadiene in 72% isolated yield. Trapping of a generated intermediate was achieved by repeating the experiment in the presence of excess styrene (20 equiv) or ethylene (1 atm), and the corresponding [4 + 2] cycloadducts of tri-tert-butylphosphacyclobutadiene were isolated in 88% and 74% yields, respectively. The platinum complex (Ph3P)2Pt(C2H4) also reacts with 1 to form an orange η2 complex of tri-tert-butylphosphacyclobutadiene in 80% isolated yield. Additionally, we report a novel method for generating a phosphinidenoid species via fluoride-induced trimethylsilyl fluoride elimination, leading to an improved preparative procedure for 1 (182 mg, 33% isolated yield).

Understanding the Nature and Properties of Hydrogen-Hydrogen Bonds: The Stability of a Bulky Phosphatetrahedrane as a Case Study.

Recently, the first mixed C/P phosphatetrahedranes (tBuC)3P and (tBuCP)2 were reported. Unlike (tBuCP)2, (tBuC)3P exhibits remarkable thermal stability, which can be partially attributed to a network of nine hydrogen-hydrogen bonds (HHBs) localized between the tert-butyl substituents. The stabilizing contribution arising from this network of HHBs was obtained from local energy decomposition (LED) analysis calculated at the domain-based local pair natural orbital CCSD(T) (DLPNO-CCSD(T)) level of theory. These calculations suggest that each HHB contributes approximately -0.7 kcal/mol of stabilization; however, the net stabilization energy likely lies between -0.25 and -0.5 kcal/mol because of steric repulsion. Spatial analysis of the London dispersion energy via a dispersion interaction density (DID) plot reveals that the DID surface is localized at key C-H groups involved in HHBs, consistent with London dispersion interactions predominantly arising from HHBs. In addition, we present a computed mechanism that supports a phosphinidenoid species as a key reaction intermediate in the synthesis of (tBuC)3P.

31P NMR Chemical Shift Tensors: Windows into Ruthenium Phosphinidene Complex Electronic Structures.

A series of octamethylcalix[4]pyrrole/ruthenium phosphinidene complexes (Na2[1=PR]) can be accessed by phosphinidene transfer from the corresponding RPA (A = C14H10, anthracene) compounds (R = tBu, iPr, OEt, NH2, NMe2, NEt2, NiPr2, NA, dimethylpiperidino). Isolation of the tert-butyl and dimethylamino derivatives allowed comparative studies of their 31P nuclear shielding tensors by magic-angle-spinning solid-state nuclear magnetic resonance spectroscopy. Density functional theory and natural chemical shielding analyses reveal the relationship between the 31P chemical shift tensor and the local ruthenium/phosphorus electronic structure. The general trend observed in the 31P isotropic chemical shifts for the ruthenium phosphinidene complexes was controlled by the degree of deshielding in the δ11 principal tensor component, which can be linked to the σRuP/πRuP* energy gap. A "δ22-δ33 crossover" effect for R = tBu was also observed, which was caused by different degrees of deshielding associated with polarizations of the σPR and σPR* natural bond orbitals.

An Azophosphine Synthetic Equivalent of Mesitylphosphaazide and Its 1,3-Dipolar Cycloaddition Reactions.

Dibenzo-7-phosphanorbornadiene-substituted diazene MesN2PA (1, where Mes = mesityl, A = anthracene, or C14H10), a synthetic equivalent of mesitylphosphaazide (MesN2P) and anthracene, was synthesized by treatment of [Ph3BPA][Na(OEt2)2] with [MesN2]OTf (OTf = CF3SO3-) in thawing tetrahydrofuran (14% isolated yield). Treatment of 1 with unsaturated molecules cyclooctyne, [Na(dioxane)2.5][OCP] (phosphaethynolate), and Ad-C≡P (Ad = adamantyl) results in the corresponding [3 + 2] phosphaazide-(phospha)alkyne cycloadducts, with concomitant loss of anthracene in 65%, 49%, and 38% isolated yield, respectively. Structural data for the phosphaethynolate cycloadduct ([3][Na(12-crown-4)2]) were obtained in a single-crystal X-ray diffraction study. A diazatriphosphole was generated by combining 1 with P2A2, a thermally activated anthracene-based molecular precursor to diphosphorus (P2). Thermolysis (33-65 °C) of 1 in benzene-d6 leads to anthracene extrusion. This process has a unimolecular kinetic profile and proceeds with activation parameters of ΔH⧧ = 21.6 ± 0.3 kcal/mol and ΔS⧧= -4.9 ± 0.8 cal/(mol K).

Taste activity in the parabrachial region in adult rats following neonatal chorda tympani transection.

The chorda tympani is a gustatory nerve that fails to regenerate if sectioned in rats 10 days of age or younger. This early denervation causes an abnormally high preference for NH4Cl in adult rats, but the impact of neonatal chorda tympani transection on the development of the gustatory hindbrain is unclear. Here, we tested the effect of neonatal chorda tympani transection (CTX) on gustatory responses in the parabrachial nucleus (PbN). We recorded in vivo extracellular spikes in single PbN units of urethane-anesthetized adult rats following CTX at P5 (chronic CTX group) or immediately prior to recording (acute CTX group). Thus, all sampled PbN neurons received indirect input from taste nerves other than the CT. Compared to acute CTX rats, chronic CTX animals had significantly higher responses to stimulation with 0.1 and 0.5 M NH4Cl, 0.1 and 0.5 M NaCl, and 0.01 M citric acid. Activity to 0.5 M sucrose and 0.01 M quinine stimulation was not significantly different between groups. Neurons from chronic CTX animals also had larger interstimulus correlations and significantly higher entropy, suggesting that neurons in this group were more likely to be activated by stimulation with multiple tastants. Although neural responses were higher in the PbN of chronic CTX rats compared to acute-sectioned controls, taste-evoked activity was much lower than observed in previous reports, suggesting permanent deficits in taste signaling. These findings demonstrate that the developing gustatory hindbrain exhibits high functional plasticity following early nerve injury.NEW & NOTEWORTHY Early and chronic loss of taste input from the chorda tympani is associated with abnormal taste behaviors. We found that compared to when the chorda tympani is sectioned acutely, chronic nerve loss leads to amplification of spared inputs in the gustatory pons, with higher response to salty and sour stimuli. Findings point to plasticity that may compensate for sensory loss, but permanent deficits in taste signaling also occur following early denervation.

Vitamin D Signaling in Gastro-Rheumatology: From Immuno-Modulation to Potential Clinical Applications.

In the last decades, the comprehension of the pathophysiology of bone metabolism and its interconnections with multiple homeostatic processes has been consistently expanded. The branch of osteoimmunology specifically investigating the link between bone and immune system has been developed. Among molecular mediators potentially relevant in this field, vitamin D has been recently pointed out, and abnormalities of the vitamin D axis have been described in both in vitro and in vivo models of inflammatory bowel diseases (IBD) and arthritis. Furthermore, vitamin D deficiency has been reported in patients affected by IBD and chronic inflammatory arthritis, thus suggesting the intriguing possibility of impacting the disease activity by the administration vitamin D supplements. In the present review, the complex interwoven link between vitamin D signaling, gut barrier integrity, microbiota composition, and the immune system was examined. Potential clinical application exploiting vitamin D pathway in the context of IBD and arthritis is presented and critically discussed. A more detailed comprehension of the vitamin D effects and interactions at molecular level would allow one to achieve a novel therapeutic approach in gastro-rheumatologic inflammatory diseases through the design of specific trials and the optimization of treatment protocols.

The Value of Hemodynamic Measurements or Cardiac MRI in the Follow-up of Patients With Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: Treatment of patients with pulmonary arterial hypertension (PAH) is conventionally based on functional plus invasive measurements obtained during right heart catheterization (RHC). Whether risk assessment during repeated measurements could also be performed on the basis of imaging parameters is unclear, as a direct comparison of strategies is lacking. RESEARCH QUESTION: How does the predictive value of noninvasive parameters compare with that of invasive hemodynamic measurements 1 year after the diagnosis of idiopathic PAH? STUDY DESIGN AND METHODS: One hundred and eighteen patients with idiopathic PAH who underwent RHC and cardiac MRI (CMR) were included in this study (median time between baseline evaluation and first parameter measures, 1.0 [0.8-1.2] years). Forty-four patients died or underwent lung transplantation. Forward Cox regression analyses were done to determine the best predictive functional, hemodynamic, and/or imaging model. Patients were classified as high risk if the event occurred < 5 years after diagnosis (n = 24), whereas patients without event were classified as low risk. RESULTS: A prognostic model based on age, sex, and absolute values at follow-up of functional parameters (6-min walk distance) performed well (Akaike information criterion [AIC], 279; concordance, 0.67). Predictive models with only hemodynamic (right atrial pressure, mixed venous oxygen saturation; AIC, 322; concordance, 0.66) or imaging parameters (right ventricular ejection fraction; AIC, 331; concordance, 0.63) at 1 year of follow-up performed similarly. The predictive value improved when functional data were combined with either hemodynamic data (AIC, 268; concordance, 0.69) or imaging data (AIC, 273; concordance, 0.70). A model composed of functional, hemodynamic, and imaging data performed only marginally better (AIC, 266; concordance, 0.69). Finally, changes between baseline and 1-year follow-up were observed for multiple hemodynamic and CMR parameters; only a change in CMR parameters was of prognostic predictive value. INTERPRETATION: At 1 year of follow-up, risk assessment based on CMR is at least equal to risk assessment based on RHC. In this study, only changes in CMR, but not hemodynamic parameters, were of prognostic predictive value during the first year of follow-up.