Fatal Herpes Simplex Esophagitis of an Infant Case Report and Review of the Literature.

ABSTRACT: Herpes simplex virus esophagitis is a rare and not readily recognized condition which is often seen in immunocompromised individuals. This case highlights the rare complication of herpes simplex virus in an otherwise healthy male infant who presented with a possible seizure after listlessness, fever, and black stools for 1 day. The decedent died shortly after arrival to the hospital emergency department, and a complete autopsy was performed, which was remarkable for upper gastrointestinal bleeding due to esophageal ulcers secondary to viral infection (herpes simplex virus type 1). To our knowledge, this is the first reported case in which herpes simplex virus esophagitis resulted in ulcerations that extended through the esophagus and involved the adjacent wall of the aorta with subsequent upper gastrointestinal bleeding leading to the death of an infant.

Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.

Progressive microcephaly and neurodegeneration are genetically heterogenous conditions, largely associated with genes that are essential for the survival of neurons. In this study, we interrogate the genetic etiology of two siblings from a non-consanguineous family with severe early onset of neurological manifestations. Whole exome sequencing identified novel compound heterozygous mutations in VARS that segregated with the proband: a missense (c.3192G>A; p.Met1064Ile) and a splice site mutation (c.1577-2A>G). The VARS gene encodes cytoplasmic valyl-tRNA synthetase (ValRS), an enzyme that is essential during eukaryotic translation. cDNA analysis on patient derived fibroblasts revealed that the splice site acceptor variant allele led to nonsense mediated decay, thus resulting in a null allele. Three-dimensional modeling of ValRS predicts that the missense mutation lies in a highly conserved region and could alter side chain packing, thus affecting tRNA binding or destabilizing the interface between the catalytic and tRNA binding domains. Further quantitation of the expression of VARS showed remarkably reduced levels of mRNA and protein in skin derived fibroblasts. Aminoacylation experiments on patient derived cells showed markedly reduced enzyme activity of ValRS suggesting the mutations to be loss of function. Bi-allelic mutations in cytoplasmic amino acyl tRNA synthetases are well-known for their role in neurodegenerative disorders, yet human disorders associated with VARS mutations have not yet been clinically well characterized. Our study describes the phenotype associated with recessive VARS mutations and further functional delineation of the pathogenicity of novel variants identified, which widens the clinical and genetic spectrum of patients with progressive microcephaly.

Electrochemical Sensing of Dopamine, Uric Acid and Ascorbic Acid Using tRGO-TiO2 Nanocomposites.

This work reports a graphene-based nonenzymatic electrochemical sensing platform for the detection of dopamine (DA), uric acid (UA), and ascorbic acid (AA). Graphene oxide, synthesized by modified Hummers method, was thermally reduced in an induction furnace at 200 °C in an Ar-H2 atmosphere to obtain thermally reduced graphene oxide (tRGO). Nanocomposites of tRGO-TiO2 were obtained by a hydrothermal method, and were characterized using Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD). FTIR spectra showed Ti-O-C peaks, indicating covalent linkage between the TiO2 nanoparticles and the reduced graphene oxide sheets. Glassy carbon electrode (GCE) was modified with the nanocomposite (tRGO-TiO2-GCE), and the modified electrode could detect dopamine (DA: 1 to 1000 µM), uric acid (UA: 1 to 900 µM), and ascorbic acid (AA: 10 to 1000 µM) in each other's presence over wide ranges, with adequate separation in peak potentials. Differential pulse voltammetry experiments yielded linear responses with sensitivities of 133.18, 33.96, and 155.59 µA mM(-1) cm(-2) for DA, UA, and AA, respectively.

Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma.

Background/aims: The aim of this study was to prospectively evaluate stereotactic body radiotherapy (SBRT) with robotic radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and methods: Patients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function [up to Child-Pugh (CP) B7] were accrued after ethical and scientific committee approval [Clinical trial registry-India (CTRI): 2022/01/050234] for treatment on robotic radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was performed for contouring, and gross tumour volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy and the duodenum max of <24 Gy). Response assessment was done at 2 months' follow-up for recanalization. Patient- and treatment-related factors were evaluated for influence in survival function. Results: Between Jan 2017 and May 2022, 318 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score: 5-7 90%, mean age: 63 years (38-85 yrs), Cancer of the Liver Italian Program <3: 84 (40%), 3-6117 (56%), infective aetiology 9.5%, performance status (PS): 0-37%; 1-56%]. Among 209 consecutive patients accrued for SBRT treatment (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow-up). At mean follow-up of 12.21 months (standard deviation: 10.66), 88 (63%) patients expired and 51 (36%) were alive. Eighty-two (59%) patients had recanalization of PVT (response), 57 (41%) patients did not recanalize and 28 (17%) had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival (OS) in responders and non-responders were 18.4 [standard error (SE): 2.52] and 9.34 month (SE 0.81), respectively (P < 0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (P = 0.019), respectively. OS in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1 and 30.3 months, respectively (P-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification stage, gender, age and RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (P-0.019). OS in patients with response to treatment, in those with no response to treatment, in those who are fit but not accrued and in those who are not suitable were 18.4, 9.34, 5.9 and 2.6 months, respectively (P-<0.001). Thirty-six of 139 patients (24%) had radiation-induced liver disease (RILD) [10 (7.2%) had classic RILD & 26 (19%) had non-classic RILD]. Derangement in CP score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after robotic radiosurgery. Eighteen (13%) had unplanned admissions, two patients required embolization due to fiducial-related bleeding and 20 (14%) had ascites, of which 9 (6%) patients required abdominocentesis. Conclusion: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Novel KIF7 mutations extend the phenotypic spectrum of acrocallosal syndrome.

BACKGROUND: Acrocallosal syndrome (ACLS) is a rare recessive disorder characterised by corpus callosum agenesis or hypoplasia, craniofacial dysmorphism, duplication of the hallux, postaxial polydactyly, and severe mental retardation. Recently, we identified mutations in KIF7, a key component of the Sonic hedgehog pathway, as being responsible for this syndrome. METHODS: We sequenced KIF7 in five suspected ACLS cases, one fetus and four patients, based on facial dysmorphism and brain anomalies. RESULTS: Seven mutations were identified at the KIF7 locus in these five cases, six of which are novel. We describe the first four compound heterozygous cases. In all patients, the diagnosis was suspected based on the craniofacial features, despite the absence of corpus callosum anomaly in one and of polydactyly in another. Hallux duplication was absent in 4/5 cases. CONCLUSIONS: These results show that ACLS has a variable expressivity and can be diagnosed even in the absence of the two major features, namely polydactyly or agenesis or hypoplasia of the corpus callosum. Facial dysmorphism with hypertelorism and prominent forehead in all the cases, as well as vermis dysgenesis with brainstem anomalies (molar tooth sign), strongly indicated the diagnosis. KIF7 should be tested in less typical patients in whom craniofacial features are suggestive of ACLS.

Prospective Evaluation of Response to Treatment, Survival Functions, Recurrence Pattern and Toxicity Profile in Indian Patients with Oligo-Brain Metastasis Treated with Only SRS.

Background: Prospective analysis of oligo-brain metastasis in Indian patients treated with SRS-only treatment. Methods: Between January 2017 and May 2022, 235 patients were screened and 138 histologically proven and radiologically confirmed. One to five brain metastasis patients aged more than 18 years with good Karnofsky performance status (KPS >70) accrued in ethical and scientific committee-approved prospective observational study protocol for treatment with only radiosurgery (SRS) with robotic radiosurgery (CyberKnife, CK) [AIMS IRB: 2020-071; CTRI No: REF/2022/01/050237]. Immobilization was performed with a thermoplastic mask, contrast CT simulation was performed with 0.625 mm slices, fused with T1 contrast/T2 FLAIR MRI images for contouring. Planning target volume (PTV) margin of 2-3 mm and a dose of 20-30 Gy in 1-5 fractions. Response to treatment, new brain lesions free survival, overall survival, and toxicity profile after CK were evaluated. Results: In total,: 138 patients with 251 lesions were accrued (median age 59 years (interquartile range [IQR] 49-67 years; female 51%; headache in 34%, motor deficit in 7%, KPS >90 in 56%; lung primary in 44%, breast in 30%; oligo-recurrence in 45%; synchronous oligo-metastases in 33%; adenocarcinoma primary in 83%). One hundred seven patients (77%) received upfront Stereotactic radiotherapy (SRS), 15 (11%) received postoperative SRS, 12 (9%) received whole brain radiotherapy (WBRT) before SRS, and 3 (2%) received WBRT plus SRS boost. The majority had solitary (56%) brain metastasis, 28% had two to three lesions, and 16% had four to five brain lesions. Frontal (39%) was the most common site. Median PTV was 15.5 mL (IQR - 8.1-28.5 mL). Seventy-one (52%) patients were treated with single fractions, 14% with three, and 33% with five fractions. Fraction schedules were 20-2 4 Gy/1fr; 27 Gy/3fr, and 25 Gy/5 fractions (mean BED 74.6 Gy [SD ± 48.1; mean MU 16608], mean treatment time was 49 min (range 17-118 min]. Twelve Gy normal brain volume was 40.8 mL (3.2%) (range 19.3-73.7 mL). At a mean follow-up of 15 months (SD 11.9 months; max 56 months), the mean actuarial OS after SRS-only treatment was 23.7 months (95% confidence interval [CI] 20-28). Further 124 (90%) patients had >3 months, 108 (78%) had >6 months, 65 (47%) had >12 months, and 26 (19%) had >24 months follow-up. Intracranial disease and extracranial disease were controlled in 72 (52.2%) and 60 (43.5%), respectively. "In-field" recurrence, "out-of-field," and "both in and out-of-field" recurrences were in 11%, 42%, and 46%, respectively. At the last follow-up, 55 patients (40%) were alive, 75 (54%) died due to disease progression, and the status of 8 (6%) patients was not known. Among 75 patients who died, 46 (61%) had extracranial disease progression, 12 (16%) had only intracranial progression, and 8 (11%) had unrelated causes. Also, 12/117 (9%) had radiological confirmation of radiation necrosis. Prognostication based on western patients (primary tumor type, number of lesions extracranial disease) showed similar outcomes. Conclusions: SRS alone in brain metastasis is feasible in the Indian subcontinent with similar survival outcomes, recurrence patterns, and toxicity as published in the western literature. Patient selection, dose schedule, and planning need to be standardized to have similar outcomes. WBRT can be safely omitted in Indian patients with oligo-brain metastasis. Western prognostication nomogram is applicable in the Indian patient population.

Synthesis, antibacterial, anti-oxidant and molecular docking studies of imidazoquinolines.

Quinoline and imidazole derivatives have been playing a significant role in functional bioactivities and were potentially used as antibacterial, antifungal, anticancer, and anti-inflammatory drugs. Owing to the limitation of drug resistance, herein we synthesized thio-, chloro-, and hydroxyl-functionalized various imidazoquinolines by molecular hybridization approach. All the imidazoquinoline derivatives were examined for their antibacterial activity against selected bacterial pathogens by the agar well diffusion method. In addition, the anti-oxidant efficacy of imidazoquinolines was also tested using ferric reducing antioxidant power (FRAP). Among them, electron-withdrawing (-Cl) substituent containing imidazoquinoline 5f showed higher antibacterial and anti-oxidant activities than other imidazoquinolines and reached the effectiveness of the standard. In addition, compounds 4f, 5e, and 3f showed moderate antibacterial activity and other derivatives displayed weak activity against various pathogens. Molecular docking studies were also performed on selected imidazoquinoline derivatives (3f, 4f, and 5f), which showed high docking score and strong binding energy values. These results revealed that thio-imidazoquinoline could assist as a prototype for the designing of multidrug-resistant antibiotics against various microbial organisms.

Hepatocellular carcinoma patients with portal vein thrombosis treated with robotic radiosurgery: Interim results of a prospective study.

BACKGROUND: This is a prospective study evaluating the role of stereotactic body radiotherapy (SBRT) with CyberKnife (CK) in Indian patients suffering from hepatocellular carcinoma with portal vein thrombosis (HCC-PVT). METHODS: Patients with inoperable HCC-PVT, good performance score (PS), and liver function are accrued for treatment on CK (version M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was done for contouring, and the gross tumor volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per-risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy, and the duodenum max of ≤24 Gy). RESULTS: Seventy-two HCC-PVT accrued till date (mean age 63 years [38-76 years], 96% male; Child-Pugh [CP] A 84%, B 9%; Barcelona-Clinic Liver Cancer [BCLC] C 96%; PS0-1: 80%, Karnofsky performance score [KPS]>70: 88%; co-morbidities 42%; infective 12%, alcohol intake 31%, adjuvant sorafenib 39%). CP scores 5, 6, 7, and 8 were in 35%, 32%, 8%, and 18%, respectively. Focal disease with portal vein thrombus (PVT) in 21%, liver involvement >50% and <50% in 46% and 32%. Liver cancer study group of Japan staging-based portal vein invasion VP2, VP3, and VP4 in 22%, 29%, and 40%. Cancer of the Liver Italian Programm (CLIP) scores 1, 2, 3, 4, and 5 were in 8%, 26%, 31%, 26%, and 7%, respectively. Mean follow-up was 7.3 months (median 6 months, standard deviation [SD] 6; range 3-30 months). Mean actuarial overall survival (OS) was 11.4 months (SE 1.587; 95% CI: 8-14.2 months). Six months and 12 months actuarial OS 55% and 38%, respectively. At last follow-up, 25/69 (36%) were alive and 44/69 (64%) were dead. Among 54 patients evaluated for response assessment, 23 (30%) had radiological confirmed PVT response, 1 (3%) had response of IVC thrombus, and 30 (42%) had no or minimal response to SBRT. Actuarial OS in responders and non-responders were 14.4 months (95% CI 9.4-19.2) and 7.4 months (95% CI 4.9-9.7), p-value: 0.022. Six and 12 months survival in responders and non-responders were 65.7% and 37% and 49% and 24.6%, respectively. Post-SBRT, 4 (12%) patients underwent transarterial chemoembolization (TACE) 3 patients (8%) and 1 patient (4%) transarterial radioembolization (TARE). Post-CK, (<4 weeks) 2 patients (4%) had decompensation. CONCLUSIONS: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Prospective evaluation of fiducial marker placement quality and toxicity in liver CyberKnife stereotactic body radiotherapy.

BACKGROUND: Evaluate morbidities and "quality" of fiducial marker placement in primary liver tumours (hepatocellular carcinoma [HCC]) for CyberKnife. MATERIALS AND METHODS: Thirty-six HCC with portal vein thrombosis(PVT) were evaluated for "quality" of fiducial placement, placement time, pain score, complications, recovery time and factors influencing placement. RESULTS: One hundred eight fiducials were placed in 36 patients. Fiducial placement radiation oncologist score was "good" in 24(67%), "fair" in 4(11%), and "poor" in 3(8%) patients. Concordance with radiologist score in "poor", "fair", and "good" score was 2/2(100%), 4/5(80%), and 24/27(89%), respectively(p=0.001). Child-Pugh score(p=0.080), performance status(PS) (p=0.014) and accrued during "learning curve"(p=0.013) affected placement score. Mean placement time(p=0.055), recovery time(p=0.025) was longer and higher major complications(p=0.009) with poor PS. Liver segment involved(p=0.484) and the Barcelona Clinic Liver Cancer(BCLC) stage did not influence placement score. "Good" placement score was 30% in first cohort whereas 93% in last cohort(p=0.023). Time for placement was 42.2 and 14.3 minutes, respectively(p=0.069). Post-fiducial pain score 0-1 in 26 patients(72%) and pain score 3-4 was in 2(6%). Five patients (14%) admitted in "day-care"(2 mild pneumothorax, 3 pain). Mortality in 1 patient(3%) admitted for hemothorax. CONCLUSION: Fiducial placement is safe and in experienced hands, "quality" of placement is "good" in majority. Major complications and admission after fiducial placement are rare. Complications, fiducial placement time, recovery time is more during the "learning curve". Poor Child-Pugh score, extensive liver involvement, poor PS have higher probability of complications.

Fragmented QRS on electrocardiography as a predictor of myocardial scar in patients with hypertrophic cardiomyopathy.

Background: Fragmented QRS (fQRS) and Q waves are ECG findings in patients with myocardial scar. fQRS is more sensitive than pathological Q waves in detecting myocardial fibrosis in patients with coronary artery disease (CAD). Cardiac magnetic resonance (CMR) imaging is used for the diagnosis and for quantifying scar tissue in patients with HCM. Our aim was to correlate ECG parameters like fQRS and Q waves with the presence of late gadolinium enhancement (LGE) assessed by contrast CMR imaging to elucidate ECG markers which might predict scar tissue in HCM.Methods: This study is a retrospective analysis which included 39 patients who were diagnosed/suspected to have HCM on echocardiography and referred for contrast CMR imaging at our centre between 2010 and 2016. Presence of fQRS was correlated with scar demonstrated by LGE on CMR.Results: Twenty four (66.67%) patients had asymmetrical septal hypertrophy, 7 (19.44%) patients had apical involvement while 5 (13.89%) had concentric pattern. Only 4 (11.11%) patients had pathological Q waves in contiguous leads on surface ECG while fQRS in two contiguous leads was present in 23 (63.89%) patients. Presence of fQRS was more in patients with LGE on CMR than those without (84.61 versus 10%, p<.001). When presence of LGE in specific segments (anterior, lateral and inferior) was correlated with corresponding ECG leads, all the three segments showed significant correlation. The overall sensitivity, specificity, PPV and NPV of fQRS for predicting scar tissue were 84.6, 90.0, 95.6 and 69.2%, respectively.Conclusion: fQRS on surface ECG can be used as an indirect marker to predict the presence of fibrosis in HCM.

Phenotypic expression and clinical outcomes in a South Asian PRKAG2 cardiomyopathy cohort.

The PRKAG2 syndrome is a rare autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), characterized by ventricular pre-excitation, progressive conduction system disease and left ventricular hypertrophy. This study describes the phenotype, genotype and clinical outcomes of a South-Asian PRKAG2 cardiomyopathy cohort over a 7-year period. Clinical, electrocardiographic, echocardiographic, and cardiac MRI data from 22 individuals with PRKAG2 variants (68% men; mean age 39.5 ± 18.1 years), identified at our HCM centre were studied prospectively. At initial evaluation, all of the patients were in NYHA functional class I or II. The maximum left ventricular wall thickness was 22.9 ± 8.7 mm and left ventricular ejection fraction was 53.4 ± 6.6%. Left ventricular hypertrophy was present in 19 individuals (86%) at baseline. 17 patients had an WPW pattern (77%). After a mean follow-up period of 7 years, 2 patients had undergone accessory pathway ablation, 8 patients (36%) underwent permanent pacemaker implantation (atrio-ventricular blocks-5; sinus node disease-2), 3 patients developed atrial fibrillation, 11 patients (50%) developed progressive worsening in NYHA functional class, and 6 patients (27%) experienced sudden cardiac death or equivalent. PRKAG2 cardiomyopathy must be considered in patients with HCM and progressive conduction system disease.

Channa brunnea, a new species of snakehead (Teleostei: Channidae) from West Bengal, India.

Channa brunnea, a new species of snakehead fish lacking pelvic fins, from West Bengal, India, is distinguished from its pelvic fin-less congeners by possessing an uniform dark brown body, ochre to bright-orange blotches on the caudal fin, fewer dorsal and anal-fin rays (35-37 vs. 47-51 and 24 vs. 28-32, respectively), fewer vertebrae (43 vs. 45-57), and fewer lateral-line scales (43-46 vs. 51-63). Though Channa brunnea superficially resembles C. bleheri, it can be distinguished from the latter by possessing dark-brown oblique markings on the upper half of the body; transverse scale rows (4½-5½ vs. 3½); pre-anal scales (22-26 vs. 17-20); 2 rows of teeth in the fifth ceratobranchial, the outer row with 16 large conical teeth (vs. 3 rows of teeth, the outer row with 13 large conical teeth); dentary with 20 large, stout, conical teeth in the inner row (vs. 32 medium-sized conical teeth); and a Kimura's two parameter (K2P) distance of 9.8-10.6%.

Proteome Based de novo Sequencing of Novel Conotoxins from Marine Molluscivorous Cone Snail Conus amadis and Neurological Activities of Its Natural Venom in Zebrafish Model.

BACKGROUND: Conus amadis is a carnivorous snail found abundantly in coastal waters of India. Despite its abundance in southern coastal waters of India and the fact that most of the conotoxin act in neuronal system, research work on Conus amadis venom was not much focused. So we have made a brief study on the venom complex of Conus amadis to identify the library of novel conotoxins and to screen the natural venom for neurological function. OBJECTIVE: De novo sequencing of novel conopeptides from the venom cocktail of Conus amadis and to screen its natural venom for the presence of biological activities in zebrafish model. METHODS: Proteome based MALDI-TOF and LC-MS-MS analysis for identification of novel conotoxins and subsequent sequencing. Due to the complex disulfide rich nature of the venom peptides, the study also involves global chemical modification experiments of the venom extract to unambiguously determine the sequence of novel conotoxins. Biological function analysis of natural venom was tested in zebrafish model to ascertain anti-epileptic properties. RESULTS: In this study, we have identified 19 novel conotoxins containing 1, 2 & 3 disulfides, belonging to different classes. Among them, 2 novel contryphans, 3 T-superfamily conotoxins, 2 A-superfamily conotoxins and 2 Mini M-Superfamily conotoxins were sequenced to its amino acid level from the fragmented spectrum of singly and doubly charged parent ions using de novo sequencing strategies. ama1054, a contryphan peptide toxin, possesses post translationally modified bromo tryptophan at its seventh position. Except ama1251, all the sequenced peptide toxins possess modified C-terminal amidation. Crude venom exhibited anticonvulsant properties in pentylenetetrazole-induced seizure in zebrafish larvae, which suggested anti-epileptic property of the venom cocktail. Acetylcholinesterase activity was also identified in the venom complex. CONCLUSION: Based on the preliminary evidence, if this study is extended further through bioassay guided purification, could possibly yield peptide toxins with anticonvulsant and other neurologically active molecules.

Characteristics of a Nationwide Voluntary Antibiotic Resistance Awareness Campaign in India; Future Paths and Pointers for Resource Limited Settings/Low and Middle Income Countries.

Antibiotic resistance has reached alarming proportions globally, prompting the World Health Organization to advise nations to take up antibiotic awareness campaigns. Several campaigns have been taken up worldwide, mostly by governments. The government of India asked manufacturers to append a 'redline' to packages of antibiotics as identification marks and conducted a campaign to inform the general public about it and appropriate antibiotic use. We investigated whether an antibiotic resistance awareness campaign could be organized voluntarily in India and determined the characteristics of the voluntarily organized campaign by administering a questionnaire to the coordinators, who participated in organizing the voluntary campaign India. The campaign characteristics were: multiple electro-physical pedagogical and participatory techniques were used, 49 physical events were organized in various parts of India that included lectures, posters, booklet/pamphlet distribution, audio and video messages, competitions, and mass contact rallies along with broadcast of messages in 11 local languages using community radio stations (CRS) spread all over India. The median values for campaign events were: expenditure-3000 Indian Rupees/day (US$~47), time for planning-1 day, program spread-4 days, program time-4 h, direct and indirect reach of the message-respectively 250 and 500 persons/event. A 2 min play entitled 'Take antibiotics as prescribed by the doctor' was broadcast 10 times/day for 5 days on CRS with listener reach of ~5 million persons. More than 85%ofcoordinators thought that the campaign created adequate awareness about appropriate antibiotic use and antibiotic resistance. The voluntary campaign has implications for resource limited settings/low and middle income countries.

Olanzapine: a new risk factor for pulmonary embolus?

Pulmonary embolus (PE) is not an uncommon cause of sudden death, and forensic pathologists are not unaccustomed to being the first to diagnose a PE in a patient, since they are often fatal. Forensic pathologists are also familiar with the known risk factors for development of PEs, including advanced age, use of oral contraceptives, smoking, obesity, a sedimentary lifestyle, postsurgery or postinjury, pregnancy, certain malignancies, factor V Leiden and prothrombin mutations, and anticardiolipin antibodies. It has recently been shown in the clinical literature that antipsychotic medications are associated with an increased risk of thromboembolic events. Clozapine, a close relative of olanzapine, has been implicated as an independent risk factor for developing a PE. Four cases have been published within the last 2 years questioning whether olanzapine may also be associated with an increased risk for PE. We report 6 cases from the Bexar County Medical Examiner's Office, occurring between 1998 and 2005 where olanzapine may have been a risk factor in the development of, and death from, PE.

Current Status of the Use of Salvaged Blood in Metastatic Spine Tumour Surgery.

To review the current status of salvaged blood transfusion (SBT) in metastatic spine tumour surgery (MSTS), with regard to its safety and efficacy, contraindications, and adverse effects. We also aimed to establish that the safety and adverse event profile of SBT is comparable and at least equal to that of allogeneic blood transfusion. MEDLINE and Scopus were used to search for relevant articles, based on keywords such as "cancer surgery," "salvaged blood," and "circulating tumor cells." We found 159 articles, of which 55 were relevant; 20 of those were excluded because they used other blood conservation techniques in addition to cell salvage. Five articles were manually selected from reference lists. In total, 40 articles were reviewed. There is sufficient evidence of the clinical safety of using salvaged blood in oncological surgery. SBT decreases the risk of postoperative infections and tumour recurrence. However, there are some limitations regarding its clinical applications, as it cannot be employed in cases of sepsis. In this review, we established that earlier studies supported the use of salvaged blood from a cell saver in conjunction with a leukocyte depletion filter (LDF). Furthermore, we highlight the recent emergence of sufficient evidence supporting the use of intraoperative cell salvage without an LDF in MSTS.

Three-dimensional-printed cardiac prototypes aid surgical decision-making and preoperative planning in selected cases of complex congenital heart diseases: Early experience and proof of concept in a resource-limited environment.

INTRODUCTION: Three-dimensional. (3D) printing is an innovative manufacturing process that allows computer-assisted conversion of 3D imaging data into physical "printouts" Healthcare applications are currently in evolution. OBJECTIVE: The objective of this study was to explore the feasibility and impact of using patient-specific 3D-printed cardiac prototypes derived from high-resolution medical imaging data (cardiac magnetic resonance imaging/computed tomography [MRI/CT]) on surgical decision-making and preoperative planning in selected cases of complex congenital heart diseases (CHDs). MATERIALS AND METHODS: Five patients with complex CHD with previously unresolved management decisions were chosen. These included two patients with complex double-outlet right ventricle, two patients with criss-cross atrioventricular connections, and one patient with congenitally corrected transposition of great arteries with pulmonary atresia. Cardiac MRI was done for all patients, cardiac CT for one; specific surgical challenges were identified. Volumetric data were used to generate patient-specific 3D models. All cases were reviewed along with their 3D models, and the impact on surgical decision-making and preoperative planning was assessed. RESULTS: Accurate life-sized 3D cardiac prototypes were successfully created for all patients. The models enabled radically improved 3D understanding of anatomy, identification of specific technical challenges, and precise surgical planning. Augmentation of existing clinical and imaging data by 3D prototypes allowed successful execution of complex surgeries for all five patients, in accordance with the preoperative planning. CONCLUSIONS: 3D-printed cardiac prototypes can radically assist decision-making, planning, and safe execution of complex congenital heart surgery by improving understanding of 3D anatomy and allowing anticipation of technical challenges.

Percutaneous transluminal angioplasty and stenting in the management of chronic mesenteric angina: A single center experience.

INTRODUCTION: The objective of our study was to review the results of percutaneous angioplasty (PTA)/stenting in the treatment of patients who presented with symptoms and angiographic findings of chronic mesenteric ischemia (CMI). MATERIALS AND METHODS: We performed a retrospective analysis of 13 consecutive patients from a single institution who underwent PTA/stenting for the treatment of symptoms suggestive of CMI. RESULTS: All 13 patients in our study were men, and most common presenting symptoms were weight loss and postprandial pain. Atherosclerosis was the most common cause. PTA and stenting was performed in 9 patients and PTA alone was done in 4 patients. Primary technical success rate was 92% with complete resolution of symptoms within 2 weeks in all patients. No statistical difference was noted in primary clinical success rate based on the number of vessels treated or the method of treatment. However, in patients whom SMA was treated had longer duration of symptom-free survival as compared to other vessels. CONCLUSION: PTA and stenting are very effective therapeutic options for patients presenting with CMI symptoms. It should be considered as the first-line of management in such patients.

Preemptive analgesia for postoperative pain relief in lumbosacral spine surgeries: a randomized controlled trial.

BACKGROUND CONTEXT: Administration of analgesic medication, before the actual onset of painful stimulus, is more effective than that after the onset of painful stimulus. This is the principle of preemptive analgesia. Although it is often considered superior to other forms of analgesia, its role in postoperative pain relief after lumbosacral spinal surgery has not been fully investigated. PURPOSE: To analyze the efficacy of preemptive analgesia with a single caudal epidural injection for patients undergoing surgeries on the lumbosacral spine by the posterior approach. STUDY DESIGN/SETTING: Randomized, double-blinded and controlled clinical trial. PATIENT SAMPLE: Eighty-two patients who underwent discectomy in the lumbosacral spine by the posterior approach, with or without instrumentation, were randomized to the control group (n=40) and to the study group (n=42). METHODS: Patients in control group received a single caudal epidural injection of 20 ml of normal saline. Patients in study group received a single caudal epidural injection of 20 ml containing bupivacaine and tramadol as the active agents. The time interval between this injection and the surgical incision was never less than 20 minutes in either of the groups. This facilitated enough time for the drug to get fixed to the nerve roots, leading to effective preemptive analgesia. OUTCOME MEASURES: Patients were monitored for postoperative pain immediately after surgery when they had completely recovered and regained consciousness from general anesthesia, and subsequently 4, 8, 12 and 24 hours thereafter. Pain was quantified using the visual analog scale (VAS) and the verbal rating scale (VRS). The time at which supplemental analgesic medication was first demanded in the postoperative period by the patient was also noted. RESULTS: The two groups were comparable for age, sex, body weight and the type of surgery they underwent. Because the data did not have a normal Gaussian distribution, the one-tailed Mann-Whitney test, being a nonparametric test, was adopted for statistical analysis. Accordingly, VAS and VRS values at all time intervals were significantly lower (p<.0001) in the study group as compared with the control group. This indicated significantly better pain relief in the study group. There was also a significant delay (p=.0041) in the first demand for supplemental analgesic medication in the postoperative period in the study group. No complication specific to the procedure was noted except for the development of postoperative urinary retention, which was transient and appropriately managed with urinary catheterization. CONCLUSIONS: Preemptive analgesia with a single caudal epidural injection of bupivacaine and tramadol is a safe, simple and effective method for postoperative pain relief.