IgG4-related disease as a variable-vessel vasculitis: A case series of 13 patients with medium-sized coronary artery involvement.

INTRODUCTION: IgG4-related disease (IgG4-RD) is a systemic autoimmune fibroinflammatory disease that can affect multiple organ systems. Although large-vessel vasculitis is a well-recognized manifestation of IgG4-RD, this condition is generally not regarded as a vasculitis. We aimed to describe coronary artery involvement (CAI), a vascular distribution about which little is known in IgG4-RD. MATERIAL AND METHODS: Patients with IgG4-related CAI were identified from a large, prospective IgG4-RD cohort. CAI was confirmed by imaging evidence of arterial or periarterial inflammation in any coronary artery. We extracted details regarding demographics, features of IgG4-RD, and manifestations of CAI. RESULTS: Of 361 cases in the cohort, 13 (4%) patients had IgG4-related CAI. All were male and all had highly-elevated serum IgG4 concentrations, with a median value of 955 mg/dL (interquartile range [IQR]: 510-1568 mg/dL; reference: 4-86 mg/dL). Median disease duration at the time of CAI diagnosis was 11 years (IQR: 8.23-15.5 years). Extensive disease in the coronary arteries was the rule: all three major coronary arteries were involved in 11 patients (85%). The coronary artery manifestations included wall thickening or periarterial soft tissue encasement (85%), stenosis (69%), calcification (69%), and aneurysms or ectasia (62%). Five patients (38%) had myocardial infarctions, 2 (15%) required coronary artery bypass grafting, and 2 (15%) developed ischemic cardiomyopathy. DISCUSSION: Coronary arteritis and periarteritis are important manifestations of IgG4-RD, which should be regarded as a variable-vessel vasculitis that is among the most diverse forms of vasculitis known. Potential complications of CAI include coronary artery aneurysms, myocardial infarction, and ischemic cardiomyopathy.

First-Row Transition Metal Complexes of a Phosphine-Silylene-Based Hybrid Ligand.

We have prepared two new silylene-phosphine-based hybrid ligands Si{N(R)C6H4(PPh2)}{PhC(NtBu)2} [R = TMS {trimethylsilyl} (1) and TBDMS {tert-butyldimethylsilyl} (2)], which possess two donor sites. Furthermore, the treatment of the bidentate ligand 1 with base metal halides {FeBr2, CoBr2, NiCl2·dme [nickel chloride(II) ethylene glycol dimethyl ether]} and 2 with NiBr2·dme [nickel bromide(II) ethylene glycol dimethyl ether] afforded four-coordinate six-membered metal complexes 3-6, respectively, which feature coordination from both Si(II) and P(III) sites. Subsequently, complexes 3 [(FeBr2)Si{N(SiMe3)C6H4(PPh2)}{PhC(NtBu)2}], 4 [(CoBr2)Si{N(SiMe3)C6H4(PPh2)}{PhC(NtBu)2}], 5 [(NiCl2)Si{N(SiMe3)C6H4(PPh2)}{PhC(NtBu)2}], and 6 [(NiBr2)Si{N(SitBuMe2)C6H4(PPh2)}{PhC(NtBu)2}] are studied for their redox and magnetic properties with the help of UV-vis spectroscopy, cyclic voltammetry, SQUID magnetometry, and theoretical calculations. Complexes 3-6 were found to display a paramagnetic behavior. All the compounds are well established by single-crystal X-ray diffraction studies.

Nickel-Catalyzed Asymmetric Hydrogenation for the Synthesis of a Key Intermediate of Sitagliptin.

Nickel-catalyzed enantioselective hydrogenation of enamines leading to the efficient synthesis of 3-R-Boc-amino-4-(2,4,5-trifluorophenyl)butyric esters, the key intermediate of the blockbuster antidiabetic drug (R)-SITAGLIPTIN, is described. The sitagliptin motifs were isolated in more than 99% yield and with 75-92% ee using the earth-abundant nickel catalyst. Upon chiral resolution with (R)- and (S)-1-phenylethylamines, the partially enantioenriched (R)- and (S)-Boc-3-amino-4-(2,4,5-trifluorophenyl)butanoic acids provided >99.5% ee of the crucial sitagliptin intermediate. The asymmetric hydrogenation protocol was scaled up to 10 g with consistency in yield and ee, and has been reproduced in multiple batches.

Comparing the Mutual Interchangeability of ECOM, FloTrac/Vigileo, 3D-TEE, and ITD-PAC Cardiac Output Measuring Systems in Coronary Artery Bypass Grafting.

OBJECTIVE: The aim of this study was to compare the mutual interchangeability of 4 cardiac output measuring devices by comparing their accuracy, precision, and trending ability. DESIGN: A single-center prospective observational study. DESIGN: Nonuniversity teaching hospital, single center. PARTICIPANTS: Forty-four consecutive patients scheduled for elective, nonemergent coronary artery bypass grafting (CABG). INTERVENTIONS: The cardiac output was measured for each participant using 4 methods: intermittent thermodilution via pulmonary artery catheter (ITD-PAC), Endotracheal Cardiac Output Monitor (ECOM), FloTrac/Vigileo System (FLOTRAC), and 3-dimensional transesophageal echocardiography (3D-TEE). MEASUREMENTS AND MAIN RESULTS: Measurements were performed simultaneously at 5 time points: presternotomy, poststernotomy, before cardiopulmonary bypass, after cardiopulmonary bypass, and after sternal closure. A series of statistical and comparison analyses including ANOVA, Pearson correlation, Bland-Altman plots, quadrant plots, and polar plots were performed, and inherent precision for each method and percent errors for mutual interchangeability were calculated. For the 6 two-by-two comparisons of the methods, the Pearson correlation coefficients (r), the percentage errors (% error), and concordance ratios (CR) were as follows: ECOM_versus_ITD-PAC (r = 0.611, % error = 53%, CR = 75%); FLOTRAC_versus_ITD-PAC (r = 0.676, % error = 49%, CR = 77%); 3D-TEE versus ITD-PAC (r = 0.538, % error = 64%, CR = 67%); FLOTRAC_versus_ECOM (r = 0.627, % error = 51%, CR = 75%); 3D-TEE_versus ECOM (r = 0.423, % error = 70%, CR = 60%), and 3D-TEE_versus_FLOTRAC (r = 0.602, % error = 59%, CR = 61%). CONCLUSIONS: Based on the recommended statistical measures of interchangeability, ECOM, FLOTRAC, and 3D-TEE are not interchangeable with each other or to the reference standard invasive ITD-PAC method in patients undergoing nonemergent cardiac bypass surgery. Despite the negative result in this study and the majority of previous studies, these less-invasive methods of CO have continued to be used in the hemodynamic management of patients. Each device has its own distinct technical features and inherent limitations; it is clear that no single device can be used universally for all patients. Therefore, different methods or devices should be chosen based on individual patient conditions, including the degree of invasiveness, measurement performance, and the ability to provide real-time, continuous CO readings.

Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment of EGFR-Mutant Non-Small-Cell Lung Cancer: Final Results From SWOG S1403.

PURPOSE: The irreversible ErbB family tyrosine kinase inhibitor (TKI) afatinib plus the EGFR monoclonal antibody cetuximab was previously shown to overcome resistance to EGFR TKIs. We studied whether the combination of afatinib plus cetuximab compared with afatinib alone would improve progression-free survival (PFS) in patients with treatment-naive EGFR-mutant non-small-cell lung cancer (NSCLC) by preventing or delaying resistance. METHODS: Patients with EGFR-mutant NSCLC without prior treatment of advanced disease were enrolled in this phase II, multicenter trial and randomly assigned to receive afatinib 40 mg orally daily plus cetuximab 500 mg/m2 intravenously every 2 weeks or afatinib alone. The primary end point was PFS. RESULTS: Between March 25, 2015 and April 23, 2018, 174 patients were randomly assigned, and 168 (83 on afatinib + cetuximab and 85 on afatinib) were eligible. There was no improvement in PFS in patients receiving afatinib plus cetuximab compared with afatinib alone (hazard ratio [HR], 1.01; 95% CI, 0.72 to 1.43; P = .94; median, 11.9 months v 13.4 months). Similarly, there was no difference in response rate (67% v 74%; P = .38) or overall survival (HR, 0.82; 95% CI, 0.50 to 1.36; P = .44). Toxicity was greater with the combination: grade ≥ 3 adverse events related to treatment occurred in 72% of patients receiving afatinib plus cetuximab compared with 40% of those receiving afatinib alone, most commonly rash and diarrhea. Dose reductions were more common in patients receiving the combination, and 30% of patients in this arm discontinued cetuximab due to toxicity. At interim analysis, there was insufficient evidence to support continued accrual, and the trial was closed. CONCLUSIONS: The addition of cetuximab to afatinib did not improve outcomes in previously untreated EGFR-mutant NSCLC, despite recognized activity in the acquired resistance setting.

Magnetic resonance imaging features in 283 patients with primary biliary cholangitis.

OBJECTIVES: To evaluate magnetic resonance imaging (MRI) features of the liver in primary biliary cholangitis (PBC). METHODS: We conducted a multicenter retrospective review on 283 patients with PBC who underwent an MRI between 2007 and 2018. Patients with overlap syndromes were excluded. MRI studies were independently reviewed by two abdominal radiologists for liver morphology, signal intensity, postcontrast enhancement, and decompensation. Liver and spleen volumes and normalized liver apparent diffusion coefficient (nlADC) were also calculated. MRI features were correlated with fibrosis stage among a subset of patients who had a liver biopsy within 6 months (n = 72). RESULTS: The study population was comprised of 283 patients (89% females) and a mean ± SD age of 59.4 ± 11.8 years. Lymphadenopathy (78.1%), periportal hyperintensity (36.7%), and periportal halo sign (27.6%) were the most common features. A positive correlation was found between fibrosis stage and spleen size (r = 0.457, p < 0.001), spleen volume (r = 0.557, p < 0.001) and portal vein diameter (r = 0.287, p = 0.013), and a negative correlation with nlADC (r = - 0.332, p = 0.011). Fibrosis stage also correlated with the presence of surface nodularity (p < 0.001), periportal halo sign (p = 0.04), collaterals (p = 0.033), and splenomegaly (p = 0.002). No significant differences in nlADC values were found in different fibrosis stages. Spleen size and volume were significantly higher in patients with ascites and collaterals (< 0.001). The periportal halo sign was present only in patients with significant fibrosis. None of the MRI features significantly correlated with inflammation grade. CONCLUSIONS: In PBC, presence of periportal halo sign correlates with significant fibrosis. Heterogeneous T2W intensity, heterogeneous postcontrast enhancement, collaterals, spleen size, and spleen volume correlate with fibrosis stage and may be useful for predicting advanced fibrosis. KEY POINTS: • The presence of periportal halo sign is indicative for significant fibrosis in primary biliary cholangitis. • Liver parenchymal heterogeneous T2 signal intensity, heterogeneous postcontrast enhancement, collaterals, spleen size, and spleen volume correlate with fibrosis stages in PBC and may be useful for predicting advanced fibrosis.

Magnetic Resonance Elastography of Liver in Light Chain Amyloidosis.

In this paper, we present our preliminary findings regarding magnetic resonance elastography (MRE) on the livers of 10 patients with systemic amyloidosis. Mean liver stiffness measurements (LSM) and spleen stiffness measurements (SSM) were obtained. Magnetic resonance imaging (MRI) images were analyzed for the distribution pattern of amyloid deposition. Pearson correlation analysis was performed in order to study the correlation between LSM, SSM, liver span, liver volume, spleen span, spleen volume, serum alkaline phosphatase (ALP), N-terminal pro b-type natriuretic peptide (NT pro BNP), and the kappa and lambda free light chains. An increase in mean LSM was seen in all patients. Pearson correlation analysis showed a statistically significant correlation between LSM and liver volume (r = 0.78, p = 0.007) and kappa chain level (r = 0.65, p = 0.04). Interestingly, LSM did not correlate significantly with SSM (r = 0.45, p = 0.18), liver span (r = 0.57, p = 0.08), or serum ALP (r = 0.60, p = 0.07). However, LSM correlated significantly with serum ALP when corrected for liver volume (partial correlation, r = 0.71, p = 0.03) and NT pro BNP levels (partial correlation, r = 0.68, p = 0.04). MRI review revealed that amyloid deposition in the liver can be diffuse, lobar, or focal. MRE is useful for the evaluation of hepatic amyloidosis and shows increased stiffness in hepatic amyloidosis. MRE has the potential to be a non-invasive quantitative imaging marker for hepatic amyloidosis.

A novel approach to suicide prevention - Educating when it matters.

BACKGROUND: Looking at the burden of suicide, there is a dire need for medical schools to incorporate suicide prevention training. Effective communication helps in early detection and management of suicidal behavior. Medical students can act as a GATEKEEPER if they receive adequate training. METHODOLOGY: This was an educational intervention study done at tertiary care teaching hospital to assess the knowledge and attitude of medical students toward depression and suicide and to impart and assess communication skills for suicide prevention in one of the four batches of students in 4th semester. Pretest was conducted to assess knowledge and attitude toward depression and suicide, followed by training using interactive lectures, demonstration of interview, and hands-on training with patients and role-plays. The posttest and objective structured clinical examination (OSCE) were administered for skill assessment. Feedback was taken regarding this intervention. RESULTS: The mean marks of the pre- and post-test were 8.96 (8.3-9.6) and 14.58 (13.8-15.3), respectively, out of 25. The difference was statistically significant (t = 13.24, P ≤ 0.0001) which suggests improvement in knowledge. We found mixed responses in attitude statements showing limited change. Mean obtained marks on OSCE examination out of 66 was 42.7. Among various components of OSCE, students scored high on rapport building. The most useful components of trainings were role-play, OSCE, and interaction with patients as per their feedback. CONCLUSION: The intervention was found effective in increasing knowledge, changing attitude, and enhancing communication skills of medical students toward suicide prevention. Training of communication skills for suicide prevention in depressed person should be given to every medical student as suggested by feedback.

Multimodal Clinical Pathway With Adductor Canal Block Decreases Hospital Length of Stay, Improves Pain Control, and Reduces Opioid Consumption in Total Knee Arthroplasty Patients: A Retrospective Review.

BACKGROUND: Total knee arthroplasty volume is increasing significantly in the United States. Reducing hospital length of stay may represent the best method for accommodating expanding volume and reducing costs. We hypothesized that tailoring a clinical pathway to facilitate early ambulation would decrease costs and resource utilization. METHODS: We conducted a sequential before-and-after study of total knee arthroplasty patients after a phased implementation of a clinical pathway that includes multimodal oral analgesic protocols, adductor canal nerve block, and standardized day of surgery ambulation protocols. Primary outcomes measured were hospital length of stay, total opioid consumption, total antiemetic use, and perioperative pain scores. RESULTS: Two hundred ninety-five patients were divided into 3 sequential cohorts. Cohort 1 received spinal anesthesia, femoral nerve block, and was not placed into postop day 0 ambulation therapy. Cohort 2 received spinal anesthesia, adductor canal block, and postop day 0 ambulation therapy. Cohort 3 received spinal anesthesia, adductor canal block, postop day 0 ambulation therapy, and standardized oral multimodal analgesic protocol. Cohort 3 had significantly reduced hospital length of stay. Cohorts 2 and 3 had significantly less opioid consumption. Cohort 3 had significantly less total ondansetron consumption compared with cohort 1. Cohort 3 had significantly reduced average pain scores compared with cohort 1. CONCLUSION: The data demonstrate that tailored clinical pathways designed to facilitate early ambulation can reduce hospital length of stay, reduce opioid consumption, reduce antiemetic use, and improve pain control. The results establish that refined clinical pathways can assist in improving care while increasing value to patients, providers, and systems.

Acute hepatozoonosis in dogs: a case report.

Two male dogs aged between 2 and 3 months belonging to German Shepherd and non descript breed were brought to Outpatient unit of Department of Veterinary Medicine, Veterinary College, Bidar with history of anorexia, weakness and going down in body condition since 15 days. Clinical examination revealed fever, enlargement of popliteal and submandibular lymph nodes, pale mucous membranes and cachectic body condition in both the cases. Haemato-biochemical examination revealed anemia, leukocytosis, thrombocytopenia, hypoalbuminemia and elevated levels of blood urea nitrogen, creatinine and alanine amino transferase. On blood smear examination, gamonts of Hepatozoon canis organisms were noticed in neutrophils. Based on these observations a diagnosis of hepatozoonosis was made. Cases were treated with Doxycycline @ 10 mg/kg, PO and uneventful recovery was noticed after 21 days of treatment.

Addition of buprenorphine to local anesthetic in adductor canal blocks after total knee arthroplasty improves postoperative pain relief: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: For the hundreds of thousands of patients who undergo total knee arthroplasty (TKA) in the United States each year, early mobilization has been demonstrated to improve functional outcomes and reduce complications. Management of postoperative pain is a critical factor in achieving early mobilization. Recent studies have shown that the use of an adductor canal block (ACB) after TKA results in increased preservation of quadriceps muscle strength, without significant difference in postoperative pain when compared to femoral nerve block. This increased preservation of quadriceps muscle strength leads to earlier mobilization. Studies have also demonstrated a prolongation of analgesia with the addition of buprenorphine to local anesthetic for regional block placement. This study examined the effect on postoperative opioid consumption when adding buprenorphine to an ACB vs an ACB with local anesthetic alone, for postoperative analgesia after unilateral TKA. METHODS: A total of 100 patients scheduled for TKA were randomized to receive postoperative ACB with local anesthetic alone or with local anesthetic and buprenorphine. The primary outcome examined was total opioid analgesic (milligrams of hydrocodone equivalent) consumption in the first 24 hours postsurgery. The secondary outcomes examined were the reported incidence of the opioid side effects nausea, vomiting, and pruritis. RESULTS: Postoperative opioid consumption decreased significantly in the group that received an ACB with local anesthetic and buprenorphine compared to an ACB with local anesthetic only (25.34±2.62 vs 35.84±2.86; P=.0076). Secondary outcomes showed no statistical difference between the 2 groups in terms of the incidence of nausea, vomiting, or pruritus. CONCLUSION: The addition of buprenorphine to an adductor canal block decreases postoperative opioid consumption when compared to an ACB with local anesthetic alone. This reduction in opioid consumption, without significant increase in side effects, makes this an attractive anesthetic adjunct for TKA.

Uncontrolled hypertension, palpitation and sweating in young female - A rare cause.

Extra-adrenal /retroperitoneal paraganglioma is a rare cause of hypertension in young with increased incidence of metastasis as compared to adrenal pheochromocytoma. We present a case of a young female with history of headache, nausea/vomiting, palpitations, uncontrolled hypertension, heat intolerance and diaphoresis. The 24-hour urine catecholamine levels were elevated. Clinical diagnosis of pheochromocytoma was made and further evaluation with Computed Tomography (CT) scan of the adrenals revealed extradrenal para-aortic retroperitoneal mass in keeping with paraganglioma. Gallium-68 DOTATE positron emission tomography-CT scan (PET-CT) confirmed the diagnosis without evidence of metastatic foci.

Incomplete removal of basal cell carcinoma: what is the value of further surgery?

INTRODUCTION: Surgical management of skin cancer is an important part of modern maxillofacial surgery. The common tumours treated are squamous cell carcinoma, malignant melanoma and some benign lesions, but the largest group of tumours are the basal cell carcinomas. Although only locally aggressive, if they are not completely removed, recurrence may occur and be troublesome, especially in the head and neck. Even in this region, incomplete excision is uncommon, less than 20 %, but management of positive margins remains controversial. This review evaluates the effectiveness of a further surgical intervention after a positive margin. MATERIALS AND METHODS: A retrospective audit was undertaken to determine the rate of positive margins within the unit and subsequently the percentage of residual tumour found in any secondary excisions. RESULTS: The results show that in a sample of 247 patients, 11 % had positive peripheral margins. A second excision only showed that 36 % had any evidence of residual tumour. DISCUSSION: The study raises the question of the value of further surgery. Finally, the authors suggest a more focused approach to the finding of a positive margin before the patient is offered more treatment.

Perception and prevalence of domestic violence in the study population.

BACKGROUND: Domestic violence is a major contributor to physical and mental ill health of the victim, and it is evident to some degree, in every society of the world. OBJECTIVES: 1) To study perception about domestic violence in the study population. 2) To compare prevalence of domestic violence within the three subgroups of the study population (i.e. spouses of psychotic patients, spouses of non-psychiatric patients and hospital staff). MATERIALS AND METHODS: A cross-sectional study was conducted among married men and women coming to Dhiraj General Hospital. Interviews were conducted using a semi-structured questionnaire. Inquiry was done about their perception regarding domestic violence, own experience any time in their life, and about the form of violence. Data was entered and analyzed using SPSS. RESULTS: 42.7% of study participants had never heard the words domestic violence. The overall prevalence of any form of violence in the study population as a whole was 32.3%. There was no significant difference found in the proportion of domestic violence among the three groups. The prevalence of physical, emotional, sexual and economic domestic violence was 16.3%, 25.3%, 2% and 11.3% respectively. Younger age group and female sex were significantly associated with the occurrence of domestic violence. CONCLUSION: Apart from the high prevalence of domestic violence in the present era, it is evident from the study that the participants' perception about domestic violence was low. Efforts should be made to raise public consciousness and reporting of domestic violence and its attendant consequences.

Noncardiac entrapment of a pulmonary artery catheter during heart transplantation: inadvertent cannulation and perforation of the internal thoracic vein.

Placement of a central venous catheter into an internal thoracic vein occurs in approximately 2% of all catheterizations. A case in which a pulmonary artery catheter was trapped within the internal thoracic vein during orthotopic heart transplantation is presented.

Different formulations of botulinum toxin type A have different migration characteristics: a double-blind, randomized study.

OBJECTIVE: Different formulations of botulinum toxin type A (BoNTA) are not identical and may behave differently in clinical practice. The reportedly lower incidence of adverse effects with one formulation (from Allergan, Ltd.) relative to another (from Ipsen, Ltd.) may be due to differences in the degree of migration of the neurotoxin-protein complex from its injection site. A double-blind, randomized, within-subject pilot study was performed to compare the migration characteristics of each formulation. METHODS: Twelve healthy volunteers were randomly assigned to receive three 0.1 mL intradermal injections in their forehead: 4 U BoNTA (Allergan) on one side, 12 U BoNTA (Ipsen) on the contralateral side, and saline in the center. At day 14, Minor's iodine starch test was performed, and the subjects walked around a hot room to induce sweating. The appearance of each forehead was documented using Canfield photography and the area of each anhidrotic halo calculated using software. RESULTS: Overall, the area of anhidrosis was significantly larger with BoNTA (Ipsen) than BoNTA (Allergan) - mean +/- SD of 2.7 +/- 0.78 cm(2) vs. 1.8 +/- 0.65 cm(2) (P = 0.005) - with the area of anhidrosis being greater with BoNTA (Ipsen) than BoNTA (Allergan) in 11 of the 12 subjects. Across all subjects, the area of anhidrosis was greater with BoNTA (Ipsen) than BoNTA (Allergan) by a mean of 77%. CONCLUSIONS: BoNTA (Ipsen) migrates more than BoNTA (Allergan) under the conditions described. The lower potential of BoNTA (Allergan) to migrate promotes more precise localization of clinical effects, thereby helping to optimize the risk/benefit ratio.