Role of rituximab as neoadjuvant therapy in a difficult case of relapsing pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare disease which involves the accumulation of insoluble lipoproteinaceous material in the alveoli leading to impaired gas exchange and even respiratory failure. Autoimmune PAP is the most common type and is characterized by the presence of anti-granulocyte-monocyte colony stimulating factor (anti GM-CSF) antibody. Whole lung lavage has been traditionally used as first-line management of PAP but there is a lack of clarity especially in the treatment of relapsing cases of PAP. Rituximab is an anti Cluster of Differentiate 20 (CD 20) monoclonal antibody that has been tried as salvage therapy for relapsing cases of PAP. We present a case of 35 years old female patient who was diagnosed as a case of relapsing PAP who was managed initially with neoadjuvant rituximab. This is a retrospective observational report showing novel use of neoadjuvant rituximab in a difficult case of relapsing PAP.

Efficacy of evidence-based institutional protocol for prevention of postoperative nausea and vomiting: A prospective observational study.

BACKGROUND: Postoperative nausea and vomiting (PONV) is the second most common complaint in the postoperative period, often resulting in increased post anaesthesia care unit (PACU) and hospital stay. Translation of knowledge into consistent practice was considered a major gap. Hence, the present study was undertaken to test the efficacy of locally developed evidence-based institutional protocol for prevention of PONV. METHODS: Phase I consisted of determining the baseline incidence of PONV before introduction of the institutional protocol for PONV prophylaxis. In phase II, educational sessions for anaesthesiologists for PONV prevention and treatment were conducted, after which an institutional protocol was introduced. In phase III, this protocol was implemented, and the incidence of PONV was recorded using the same methodology as in phase I. The rate of adherence to the institutional protocol was also recorded. RESULTS: The incidence of postoperative nausea (PON) dropped significantly from 32.5% in phase I to 20% in phase III (p = 0.033). Similarly, the incidence of postoperative vomiting (POV) decreased from 20.5% in phase I to 9.1% in phase III (p = 0.016). Of all anaesthesiologists, 78.18% were noted to adhere to the protocol in phase III. Incidence of PON and POV was significantly less in patients in whom PONV prophylaxis was administered in adherence to protocol (8.3% vs 57.7%, p < 0.001; 3.6% vs 26.9%, p < 0.001, respectively). CONCLUSION: Evidence-based institutional protocols are effective in significantly reducing the incidence of PONV in adults undergoing noncardiac surgery under anaesthesia. CLINICAL TRIAL NUMBER AND REGISTRY URL: The trial was registered with Clinical Trials Registry of India (http:/ctri.nic.in) (CTRI/2015/12/006432).

Role of Transesophageal and Epicardial Echocardiography to Assess Surgical Repair in Double-Outlet Left Ventricle.

A double-outlet left ventricle (DOLV) is a congenital cardiac anomaly that rarely is encountered. This case report demonstrates the echocardiographic features of DOLV in the form of the pulmonary artery arising completely from the left ventricle with D-looped ventricles, especially when evaluated by intraoperative transesophageal echocardiography (TEE), along with the correlation of characteristic features with cardiac computerized tomography. The features pertinent to the differentiation of DOLV from double-outlet right ventricle and congenitally corrected transposition of the great arteries by echocardiography have been described. To the authors' knowledge, this was the first report of intraoperative TEE in the case of DOLV. In addition, the use of intraoperative echocardiography to rule out coronary compression as a cause for post-repair ventricular tachycardia, by use of TEE to rule out ventricular dysfunction and regional wall motion abnormalities, as well as epicardial echocardiography to demonstrate normal coronary blood flow, has been reported.

Bi-ventricular repair of double outlet left ventricle: Experience and review of the literature.

BACKGROUND: Double-outlet left ventricle (DOLV) is a rare congenital cardiac anomaly. The aorta and the main pulmonary arterial trunk arises predominantly from the left ventricle and is associated with a malaligned ventricular septal defect, various degrees of hypoplasia of the right ventricle, and presence, or absence of pulmonary stenosis. Bi-ventricular repair is the preferred treatment option whenever possible. Multiple techniques for bi-ventricular repair have been described. The best option for DOLV correction is by translocating the pulmonary root from the left ventricle to the right ventricle. In this series, we report four patients who underwent biventricular repair of DOLV with excellent outcomes. METHODS: This is a retrospective study of four patients who underwent surgical correction of DOLV between January 2014 and December 2018. We collected all patient details from the institute patient record system. Echocardiographic data were obtained from the records. Intraoperative charts were reviewed for further information on the surgical procedure and cardiopulmonary bypass. Postoperative data included survival, functional status, and followup echocardiography. RESULTS: Of the four children, three underwent pulmonary root translocation, and one child underwent a Reparation al etage Ventriculaire (REV) procedure. There was no mortality in our series, and all children are in a stable clinical condition in the recent follow-up, and no re-operations or interventions were required following primary surgical correction. CONCLUSION: DOLV is anatomically and surgically a challenging subset. Pulmonary root translocation in this anatomy is technically challenging but safe and superior option when compared to other alternative surgical procedures. Pulmonary root translocation can be performed with excellent results, even in infants.

Rheumatoid arthritis synovial microenvironment induces metabolic and functional adaptations in dendritic cells.

Rheumatoid arthritis (RA) is a chronic autoimmune disease which causes degradation of cartilage and bone. It is well appreciated that the pathogenic hallmark of RA is the mass influx of inflammatory cells into the joint. However, the role that dendritic cells (DC) may play in this inflammatory milieu is still relatively unexplored. Moreover, the contribution this unique synovial microenvironment has on DC maturation is still unknown. Using monocyte-derived DC (MoDC), we established an in-vitro model to recapitulate the synovial microenvironment to explore DC maturation. MoDC treated with conditioned media from ex-vivo synovial tissue biopsy cultures [explant-conditioned media (ECM)] have increased expression of proinflammatory cytokines, chemokines and adhesion molecules. ECM DC have increased expression of CD83 and CC-chemokine receptor (CCR)7 and decreased expression of CCR5 and phagocytic capacity, suggestive of heightened DC maturation. ECM-induced maturation is concomitant with altered cellular bioenergetics, whereby increased expression of glycolytic genes and increased glucose uptake are observed in ECM DC. Collectively, this results in a metabolic shift in DC metabolism in favour of glycolysis. These adaptations are in-part mediated via signal transducer and activator of transcription-3 (STAT-3), as demonstrated by decreased expression of proinflammatory cytokines and glycolytic genes in ECM DC in response to STAT-3 inhibition. Finally, to translate these data to a more in-vivo clinically relevant setting, RNA-seq was performed on RA synovial fluid and peripheral blood. We identified enhanced expression of a number of glycolytic genes in synovial CD1c+ DC compared to CD1c+ DC in circulation. Collectively, our data suggest that the synovial microenvironment in RA contributes to DC maturation and metabolic reprogramming.

'Where did the tube go?' A case of retropharyngeal submucosal false passage during nasal intubation.

Nasotracheal intubation could be associated with a variety of complications, of which traumatic complications are commonly encountered. We present a rare case of retropharyngeal submucosal false passage which occurred during nasotracheal intubation inspite of avoiding potential risk factors known for causing nasopharyngeal trauma. Risk factors, preventive measures and probable reason for this complication have been discussed.

Pulmonary Calcifications: Is it an Entity in the New World Dialysis Patient?

Metastatic pulmonary calcification (MPC) has been described in the literature to affect up to 60% of dialysis patients. Several case series of MPC were described in 1960s and 1970s. Patients are generally asymptomatic or may present with acute respiratory distress. This entity is associated with up to 60% mortality. We hereby report a case of chronic kidney disease on maintenance hemodialysis who presented with unexplained recurrent dyspnea despite adequate hemodialysis. She was evaluated and found to have a rare presentation of calciphylaxis.

A prospective genome-wide study of prostate cancer metastases reveals association of wnt pathway activation and increased cell cycle proliferation with primary resistance to abiraterone acetate-prednisone.

Background: Genomic aberrations have been identified in metastatic castration-resistant prostate cancer (mCRPC), but molecular predictors of resistance to abiraterone acetate/prednisone (AA/P) treatment are not known. Patients and methods: In a prospective clinical trial, mCRPC patients underwent whole-exome sequencing (n = 82) and RNA sequencing (n = 75) of metastatic biopsies before initiating AA/P with the objective of identifying genomic alterations associated with resistance to AA/P. Primary resistance was determined at 12 weeks of treatment using criteria for progression that included serum prostate-specific antigen measurement, bone and computerized tomography imaging and symptom assessments. Acquired resistance was determined using the end point of time to treatment change (TTTC), defined as time from enrollment until change in treatment from progressive disease. Associations of genomic and transcriptomic alterations with primary resistance were determined using logistic regression, Fisher's exact test, single and multivariate analyses. Cox regression models were utilized for determining association of genomic and transcriptomic alterations with TTTC. Results: At 12 weeks, 32 patients in the cohort had progressed (nonresponders). Median study follow-up was 32.1 months by which time 58 patients had switched treatments due to progression. Median TTTC was 10.1 months (interquartile range: 4.4-24.1). Genes in the Wnt/ß-catenin pathway were more frequently mutated and negative regulators of Wnt/ß-catenin signaling were more frequently deleted or displayed reduced mRNA expression in nonresponders. Additionally, mRNA expression of cell cycle regulatory genes was increased in nonresponders. In multivariate models, increased cell cycle proliferation scores (≥ 50) were associated with shorter TTTC (hazard ratio = 2.11, 95% confidence interval: 1.17-3.80; P = 0.01). Conclusions: Wnt/ß-catenin pathway activation and increased cell cycle progression scores can serve as molecular markers for predicting resistance to AA/P therapy.

Dengue Fever-induced Thrombotic Microangiopathy: An Unusual Cause of Renal Failure.

Dengue fever is a tropical infection, which is mosquito-borne disease, caused by dengue virus and spread by Aedes mosquitoes. The incidence of dengue fever has risen rapidly over the past few years. About half of dengue infections are asymptomatic, and a great majority present with fever and body ache. However, the occurrence of complications is well known, including acute kidney injury (AKI). AKI in dengue is usually attributable to a pre-renal cause. Thrombotic microangiopathy is an extremely rare complication of dengue fever, with only a few published case reports in medical literature. This case intends to highlight the importance of recognizing dengue fever-induced thrombotic microangiopathy by physicians and pathologists, enabling better diagnosis and management of this life-threatening condition.

Identification of therapeutic targets for glioblastoma by network analysis.

Glioblastoma can originate from terminally differentiated astrocytes and neurons, which can dedifferentiate to a stem cell-like state upon transformation. In this study, we confirmed that transformed dedifferentiated astrocytes and neurons acquired a stem/progenitor cell state, although they still retained gene expression memory from their parental cell. Transcriptional network analysis on these cells identified upregulated genes in three main pathways: Wnt signaling, cell cycle and focal adhesion with the gene Spp1, also known as osteopontin (OPN) serving as a key common node connecting these three pathways. Inhibition of OPN blocked the formation of neurospheres, affected the proliferative capacity of transformed neurons and reduced the expression levels of neural stem cell markers. Specific inhibition of OPN in both murine and human glioma tumors prolonged mice survival. We conclude that OPN is an important player in dedifferentiation of cells during tumor formation, hence its inhibition can be a therapeutic target for glioblastoma.

Widespread non-adherence to evidence-based maternity care guidelines: a population-based cluster randomised household survey.

OBJECTIVE: To assess the quality of maternity care in an Indian metropolitan city. STUDY DESIGN: Three-stage cluster randomised cross-sectional survey. SETTING: Sixty selected colonies of Delhi. POPULATION: One thousand eight hundred and one subjects (of 2286 eligible) were enrolled from 118 446 houses. Women who had delivered a live viable birth in the past 6 months were selected for the study. METHODS: In stage 1, 20 wards (of 150) were selected using a probability-proportionate-to-size systematic method. In stage 2, one colony from each income stratum (high, middle and low) was selected from each ward by simple random sampling. In stage 3, a house-to-house survey was conducted to recruit 30 women for administering a peer-reviewed and pilot-trialled questionnaire. MAIN OUTCOME MEASURES: Caesarean section rate, induction rate and episiotomy rate. RESULTS: National health targets such as iron supplementation advice (>96%), tetanus vaccination (>81%), and ≥3 antenatal visits (>90%) were largely achieved across health care facilities but not in home deliveries. Interventions were lower in public than private hospitals: caesarean section [23.7% (20.2-27.7) versus 53.8% (49.3-58.3)], induction [20.6% (17.5-24.25) versus 30.8% (26.8-33.2)] and episiotomy [57.8% (52.3-63.1) versus 79.4% (71.0-85.9)]. Private hospitals achieved better labour support rates [1.1% (0.5-2.2) versus 14.6% (8.5-24.1)] and pain relief [0.9% (0.4-2.0) versus 9.9 (6.5-14.8)]. Pubic hair shaving [16.2% (11.5-22.5) versus 36.4% (29.9-43.4)], enema [20.2% (15.5-26.0) versus 57.3% (49.5-64.8)], and IV fluids during labour [44.0% (36.2-52.2) versus 38.7% (29.3-49.1)] were widely prevalent in public and private hospitals. CONCLUSION: Present practices fall short of evidence-based guidelines, with relative overuse of interventions in private hospitals and deficiency of patient-centred practices such as labour support in public hospitals.

Esophageal distension during bolus transport: can it be detected by intraluminal impedance recordings?

BACKGROUND: Esophageal multiple intraluminal impedance (MII) measurement has been used to detect gastro-esophageal reflux and bolus transport. It is not clear if MII can detect changes in luminal cross sectional area (CSA) during bolus transport. Intraluminal ultrasound (US) images, MII, and high resolution manometry (HRM) were recorded simultaneously to determine temporal relationship between CSA and impedance during esophageal bolus transport and to define the relationship between peak distension and nadir impedance. METHODS: Studies were conducted in five healthy subjects. MII, HRM, and US images were recorded 6 cm above LES. Esophageal distensions were studied during swallows and injections of 0.5 N saline bolus into the esophagus. KEY RESULTS: Temporal change in esophageal CSA correlates with changes in impedance (r-value: mean ± SD = -0.80 ± 0.08, range: -0.94 to -0.66). Drop in impedance during distension occurs as a two-step process; initial large drop associated with onset of CSA increase, followed by a small drop during which majority of the CSA increase occurs. Peak CSA and nadir impedance occur within 1 s of each other. Increase in swallow and injection volumes increased the CSA, had no effect on large drop but increased the small drop amplitude. We observed a significant correlation between peak CSA and nadir impedance (r = -0.90, p < 0.001) and a better correlation between peak CSA and inverse impedance (r = 0.94, p < 0.001). CONCLUSIONS & INFERENCES: Further studies are needed to confirm that intraluminal impedance recordings may be used to measure luminal CSA during esophageal bolus transport.