Correlation of fraction of exhaled nitric oxide with asthma control test and asthma severity in diagnosed cases of asthma.

Background: Fraction of NO in exhaled air (FENO) has emerged as a simple, non-invasive, sensitive marker of airway inflammation in asthma diagnosis and management. Correlation studies of FENO with clinical grades of asthma and symptom burden are sparse, more so in Indian population. Hence, this study was carried out in Indian subjects to evaluate FENO correlation with asthma severity. Methods: The study was performed on 52 proven cases of asthma in the age group of 17-90 years in period of December 2016 to May 2018. All the subjects had assessment in the form of Asthma Control Test (ACT)questionnaire, FENO parts per billion measurement with a portable NO analyzer (NIOX MINO Airway Inflammation Monitor; Aerocrine) and spirometry. Statistical analysis was presented in the form of percentage (%) and mean. Results: Of a total of 52 asthma cases, 27 (51.9%) were male cases while 25 (48.1%) were female cases. Study population ranged from 17 to 82 years. Subjects categorized into 03 categories of asthma severity based on their treatment step. ACT score of ranged between 11 and 25 with a mean value of 20.27 and standard deviation of 3.73. No significant correlation was found between FENO and ACT (r) = -0.177, P-value = 0.210 (>0.05). Significant correlation between FENO and different grades of asthma severity was found with p-value 0.032 (<0.05). Conclusion: Asthma severity as assessed by the step of treatment is correlated well with FENO value in an asthmatic individual to maintain the controlled asthma status. FENO and ACT were found to have no correlation.

Phenytoin-induced organising pneumonia: An unknown entity.

Organising pneumonia can be idiopathic or as a result of other inciting factors such as drugs. Phenytoin has been implicated in significant side effects predominantly involving extrapulmonary sites. Pulmonary side effects are reported less frequently. Hereby, we report a first case of phenytoin-induced organising pneumonia from India and evidence of significant improvement after stopping the drug.

Bronchoscopic device closure of postoperative bronchopleural fistulae: Novel devices and innovative techniques.

BACKGROUND: Bronchoscopic device closure plays a significant role in the nonsurgical management of bronchopleural fistulae (BPF). Herein, we describe our 10-year experience in the management of postoperative BPF using various device closure modalities. This is the largest series of bronchoscopic device closure of BPF being reported from India. MATERIALS AND METHODS: This was a retrospective analysis of data of patients who underwent bronchoscopic device closure with various techniques for the management of postoperative BPF. In total, 11 patients (six males and five females) with a mean age (±standard deviation) of 42.72 ± 14.40 years with BPFs were treated with various bronchoscopic interventions for BPF closure. We used various devices such as endobronchial coils, occluder devices, and covered tracheobronchial self-expandable stents for BPF closure depending on the size of air leaks. We describe the various devices used, technique, and outcome of bronchoscopic management of BPF. RESULTS: All our patients had developed BPFs postoperatively. Pulmonary tuberculosis was the most common etiology seen in nine of our patients. All the devices were placed using a fiberoptic bronchoscope, and all patients were followed up for a minimum duration of 6 months. We successfully localized and closed BPFs in nine (81.81%) of our patients. CONCLUSIONS: Bronchoscopic device closure can be a successful strategy to manage postoperative BPF with minimal complications.

Pilot Study to Assess Safety and Usability of the Kyron NPWT System.

There is an evident need for Negative Pressure Wound Therapy (NPWT) systems specifically designed for use in resource-constrained settings to aid in the treatment of open wounds. METHODS: Prospective single-arm interventional pilot study of 14 patients with complex wounds was conducted at Kirtipur Hospital in Kathmandu, Nepal. A novel NPWT device, the Kyron Suction Unit, was used by 4 plastic surgeons. Primary outcomes were ease of use (10-point Likert scale) and device safety (adverse events recorded). Pain (Visual Analogue Scale score), quality of life (modified EuroQol Derived Single Index scores), and wound dimensions were recorded. RESULTS: User ratings on the 10-point Likert scale indicated high confidence and ease of use: median confidence setting up the device of 1.0 [interquartile range (IQR), 1.0; mean 2.3], median confidence maintaining the device of 1.0 (IQR, 1.0; mean, 1.5), and median ease of disassembly of 1.0 (IQR, 1.0; mean, 1.4). Significant improvement in Visual Analogue Scale scores (P = 0.03), modified EuroQol Derived Single Index scores (P < 0.001), and a reduction in wound volume [median, 47.25-9.75 cm3 (P = 0.01)]. Image analysis of wounds pretreatment and posttreatment demonstrated increase in granulation tissue surface area [median, 7.6-28.7 cm2 (P = 0.003)] and decrease in open wound surface area [median, 48.33-33.6 cm2 (P = 0.01)]. CONCLUSIONS: The Kyron Suction Unit was safe and easily managed by plastic surgeons. The device design promoted access to NPWT, a therapy proven to reduce healing time and decrease complications for patients with open wounds, in a resource-constrained setting.

Bronchial artery embolization in treatment of hemoptysis: Treatment efficacy and complications at a tertiary care chest centre.

BACKGROUND: Hemoptysis is one of the most alarming condition to both the patients suffering from it and the treating physicians. It is caused due to varied etiologies. One of the emergent and at times life-saving treatment option is by minimally invasive interventional radiological technique of Bronchial Atery Embolization (BAE). The authors aimed to carry out a retrospective analysis of short term efficacy and safety of all patients treated by this technique at a tertiary care thoracic centre. METHODS: A total of 52 patients were included in the study who had a median follow up of 35 days. All these patients were referred for hemoptysis, intractable hemoptysis not controlled by conservative management or massive hemoptysis. An analysis of the underlying etiology, immediate and short term outcomes and complications was made. RESULTS: The study showed Tuberculosis and its sequel (bronchiectasis and chronic fibrotic changes) as the commonest etiology (65%). The BAE showed high short term efficacy (92%) in stopping the hemoptysis with a relatively low complication rate especially of major complications such as spinal cord ischemia (1.9%). The study strengthens the limited Indian data available on the subject and based on its outcome, BAE should be tried in all patients presenting with uncontrollable or massive hemoptysis not getting relief by conservative management alone. CONCLUSION: BAE is a very effective procedure with very less complications for management of massive or uncontrollable hemoptysis.

Pharmacokinetics, biodistribution and antitumour effects of Sclerotium rolfsii lectin in mice.

Sclerotium rolfsii lectin (SRL) is a lectin isolated from the fungus Sclerotium rolfsii and has exquisite binding specificity towards the oncofetal Thomsen-Friedenreich antigen (TF-Ag; Galß1-3GalNAcα-O-Ser/Thr) and its derivatives. Previous studies have shown that SRL inhibits the proliferation of human colon, breast and ovarian cancer cells in vitro and suppresses tumour growth in mice when introduced intratumourally. The present study assessed the effect of SRL on tumour growth when introduced intraperitoneally in BALB/c nude mice and investigated the pharmacokinetics and biodistribution of SRL in Swiss albino mice. When 9 doses of SRL (30 mg/kg body weight/mice) was administered to BALB/c nude mice bearing human colon cancer HT-29 xenografts, a substantial reduction in tumour size was observed. A 35.8% reduction in tumour size was noted in the treated animals after 17 days. SRL treatment also inhibited angiogenesis, and the tumours from the treated animals were observed to carry fewer blood vessels and express less angiogenesis marker protein CD31, than that from the control animals. Pharmacokinetics and biodistribution analysis revealed that SRL was detected in the serum after 1 h and its level peaked after 24 h. SRL was not detected in any of the organs apart from the kidney where a trace amount was detected after 24 h of SRL injection. No significant changes were observed in any of the biochemical parameters tested including SGOT, SGPT, LDH, CREAT and BUN in the SRL-treated mice compared to these levels in the controls. This suggests that SRL has good potential to be developed as a therapeutic agent for cancer treatment and warrant further investigations in vivo and subsequent clinical trials.

Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot.

The use of radiosensitizers in clinical radiotherapy is limited by systemic toxicity. The biopolymeric, biodegradable, injectable liposome-in-gel-paclitaxel (LG-PTX) system was developed for regional delivery of the radiosensitizer paclitaxel (PTX), and its efficacy was evaluated with concurrent fractionated radiation. LG-PTX is composed of nano-sized drug-loaded fluidizing liposomes, which are incorporated into a porous biodegradable gellan hydrogel. This allows enhanced drug permeation while maintaining a localization of the drug depot. LG-PTX had an IC50 of 325±117 nM in B16F10 melanoma cells, and cytotoxicity with concurrent doses of fractionated radiation showed significant increase in apoptotic cells (75%) compared to radiation (39%) or LG-PTX (43%) alone. Peri-tumoral injection in tumor-bearing mice showed PTX localization in the tumor 2 hours after administration, with no drug detected in plasma or other organs. LG-PTX administration with doses of focal radiation (5×3 Gy) significantly reduced tumor volumes compared to control (6.4 times) and radiation alone (1.6 times) and improved animal survival. LG-PTX thus efficiently localizes the drug at the tumor site and synergistically enhances the effect of concurrent radiotherapy. This novel liposome-in-gel system can potentially be used as a platform technology for the delivery of radiosensitizing drugs to enhance the efficacy of chemoradiotherapy.

Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open-label, two-centre, randomised controlled trial.

BACKGROUND: Because treatment with third-generation cephalosporins is associated with slow clinical improvement and high relapse burden for enteric fever, whereas the fluoroquinolone gatifloxacin is associated with rapid fever clearance and low relapse burden, we postulated that gatifloxacin would be superior to the cephalosporin ceftriaxone in treating enteric fever. METHODS: We did an open-label, randomised, controlled, superiority trial at two hospitals in the Kathmandu valley, Nepal. Eligible participants were children (aged 2-13 years) and adult (aged 14-45 years) with criteria for suspected enteric fever (body temperature ≥38·0°C for ≥4 days without a focus of infection). We randomly assigned eligible patients (1:1) without stratification to 7 days of either oral gatifloxacin (10 mg/kg per day) or intravenous ceftriaxone (60 mg/kg up to 2 g per day for patients aged 2-13 years, or 2 g per day for patients aged ≥14 years). The randomisation list was computer-generated using blocks of four and six. The primary outcome was a composite of treatment failure, defined as the occurrence of at least one of the following: fever clearance time of more than 7 days after treatment initiation; the need for rescue treatment on day 8; microbiological failure (ie, blood cultures positive for Salmonella enterica serotype Typhi, or Paratyphi A, B, or C) on day 8; or relapse or disease-related complications within 28 days of treatment initiation. We did the analyses in the modified intention-to-treat population, and subpopulations with either confirmed blood-culture positivity, or blood-culture negativity. The trial was powered to detect an increase of 20% in the risk of failure. This trial was registered at ClinicalTrials.gov, number NCT01421693, and is now closed. FINDINGS: Between Sept 18, 2011, and July 14, 2014, we screened 725 patients for eligibility. On July 14, 2014, the trial was stopped early by the data safety and monitoring board because S Typhi strains with high-level resistance to ciprofloxacin and gatifloxacin had emerged. At this point, 239 were in the modified intention-to-treat population (120 assigned to gatifloxacin, 119 to ceftriaxone). 18 (15%) patients who received gatifloxacin had treatment failure, compared with 19 (16%) who received ceftriaxone (hazard ratio [HR] 1·04 [95% CI 0·55-1·98]; p=0·91). In the culture-confirmed population, 16 (26%) of 62 patients who received gatifloxacin failed treatment, compared with four (7%) of 54 who received ceftriaxone (HR 0·24 [95% CI 0·08-0·73]; p=0·01). Treatment failure was associated with the emergence of S Typhi exhibiting resistance against fluoroquinolones, requiring the trial to be stopped. By contrast, in patients with a negative blood culture, only two (3%) of 58 who received gatifloxacin failed treatment versus 15 (23%) of 65 who received ceftriaxone (HR 7·50 [95% CI 1·71-32·80]; p=0·01). A similar number of non-serious adverse events occurred in each treatment group, and no serious events were reported. INTERPRETATION: Our results suggest that fluoroquinolones should no longer be used for treatment of enteric fever in Nepal. Additionally, under our study conditions, ceftriaxone was suboptimum in a high proportion of patients with culture-negative enteric fever. Since antimicrobials, specifically fluoroquinolones, are one of the only routinely used control measures for enteric fever, the assessment of novel diagnostics, new treatment options, and use of existing vaccines and development of next-generation vaccines are now a high priority. FUNDING: Wellcome Trust and Li Ka Shing Foundation.

Risk Factors For Necrotizing Fasciitis And Its Outcome At A Tertiary Care Centre.

BACKGROUND: Necrotizing fasciitis (NF) is a serious and potentially fatal condition where there is rapid progression of inflammation of skin, subcutaneous tissue, and superficial fascia and can be mono-microbial or poly-microbial. The disease is rapidly progressive in nature and if not promptly treated leads to significant morbidity or even mortality. This study was designed to explore the various risk factors commonly present and study the outcome of the disease. METHODS: This was a cross sectional study done in tertiary centre over period of one year from April 2014 to March 2015. Patient admitted with soft tissue infection were presumptively made diagnosis of NF based on clinical features and final diagnosis was made after pre-operative surgical findings. RESULTS: Forty two (40.38%) patients had final diagnosis of NF out of 102 soft tissue infections. Twentynine (69%) of 42 patients with NF fully recovered with surgical and medical management. Eleven (26.2%) of these patients succumbed to their illness and two (4.8%) needed amputation of limb to control the infection. The most common co-morbid condition was alcoholism, followed by diabetes mellitus. CONCLUSIONS: The incidence of necrotizing fasciitis in patients admitted with soft tissue infection was 40.38%. Mortality and morbidity due to this condition was found to be high.

Synthesis and Preclinical Evaluation of (177)Lu-CHX-A"-DTPA-Rituximab as a Radioimmunotherapeutic Agent for Non-Hodgkin's Lymphoma.

INTRODUCTION: Radioimmunotherapy is a feasible treatment modality for B-cell lymphomas expressing CD20 antigen. Tagging of anti-CD20 monoclonal antibody with a ß(-) emitter will deliver radiation to the tumor preferentially, thereby causing its destruction. This work explores the utility of (177)Lu-CHX-A"-DTPA-Rituximab as a radioimmunotherapeutic agent for non-Hodgkin's lymphoma (NHL). METHODS: Rituximab was conjugated with p-NCS-Bn-CHX-A"-DTPA and radiolabeled with (177)Lu. (177)Lu-CHX-A"-DTPA-Rituximab was characterized by SE-HPLC. In vitro cell binding and inhibition studies were carried out in Raji cells which express CD20 antigen. Biodistribution studies were performed in SCID mice bearing lymphoma at various time intervals. RESULTS: The CHX-A"-DTPA-Rituximab conjugate prepared had three molecules of DTPA per Rituximab molecule. Radiochemical purity of (177)Lu-CHX-A"-DTPA-Rituximab was >95%. In the HPLC system, (177)Lu-CHX-A"-DTPA-Rituximab showed a single peak (Rt ∼15.5 minutes). In vitro cell binding studies showed 38.9%±1.1% binding of (177)Lu-CHX-A"-DTPA-Rituximab (∼6.7 nM of radioimmunoconjugate) with Raji cells which reduced to 17.7%±0.5% with the addition of 67 nM of cold antibody. Biodistribution studies showed good tumor uptake at all the time points studied. CONCLUSIONS: In vitro and in vivo studies showed good specificity of (177)Lu-CHX-A"-DTPA-Rituximab toward CD20 antigen. It can be concluded that (177)Lu-CHX-A"-DTPA-Rituximab could be a promising agent in the treatment of NHL.

Gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever in Nepal: an open-label, randomized, controlled trial.

BACKGROUND: Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A. METHODOLOGY AND PRINCIPAL FINDINGS: Adults and children clinically diagnosed with uncomplicated enteric fever were enrolled in the study to receive gatifloxacin (10 mg/kg/day) in a single dose or ofloxacin (20 mg/kg/day) in two divided doses for 7 days. Patients were followed for six months. The primary outcome was treatment failure in patients infected with nalidixic acid resistant isolates. 627 patients with a median age of 17 (IQR 9-23) years were randomised. Of the 218 patients with culture confirmed enteric fever, 170 patients were infected with nalidixic acid-resistant isolates. In the ofloxacin group, 6 out of 83 patients had treatment failure compared to 5 out of 87 in the gatifloxacin group (hazard ratio [HR] of time to failure 0.81, 95% CI 0.25 to 2.65, p = 0.73). The median time to fever clearance was 4.70 days (IQR 2.98-5.90) in the ofloxacin group versus 3.31 days (IQR 2.29-4.75) in the gatifloxacin group (HR = 1.59, 95% CI 1.16 to 2.18, p = 0.004). The results in all blood culture-confirmed patients and all randomized patients were comparable. CONCLUSION: Gatifloxacin was not superior to ofloxacin in preventing failure, but use of gatifloxacin did result in more prompt fever clearance time compared to ofloxacin. TRIAL REGISTRATION: ISRCTN 63006567 (www.controlled-trials.com).

Aetiologies of central nervous system infections in adults in Kathmandu, Nepal: a prospective hospital-based study.

We conducted a prospective hospital based study from February 2009-April 2011 to identify the possible pathogens of central nervous system (CNS) infections in adults admitted to a tertiary referral hospital (Patan Hospital) in Kathmandu, Nepal. The pathogens of CNS infections were confirmed in cerebrospinal fluid (CSF) using molecular diagnostics, culture (bacteria) and serology. 87 patients were recruited for the study and the etiological diagnosis was established in 38% (n = 33). The bacterial pathogens identified were Neisseria meningitidis (n = 6); Streptococcus pneumoniae (n = 5) and Staphylococcus aureus (n = 2) in 13/87(14%). Enteroviruses were found in 12/87 (13%); Herpes Simplex virus (HSV) in 2/87(2%). IgM against Japanese encephalitis virus (JEV) was detected in the CSF of 11/73 (15%) tested samples. This is the first prospective molecular and serology based CSF analysis in adults with CNS infections in Kathmandu, Nepal. JEV and enteroviruses were the most commonly detected pathogens in this setting.

Evaluation of an electricity-free, culture-based approach for detecting typhoidal Salmonella bacteremia during enteric fever in a high burden, resource-limited setting.

BACKGROUND: In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella. METHODOLOGY/PRINCIPAL FINDINGS: Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%-97.0%) and 96.0% (92.7%-98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months. CONCLUSIONS/SIGNIFICANCE: A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories.

Comparative study of extended versus short term thromboprophylaxis in patients undergoing elective total hip and knee arthroplasty in Indian population.

BACKGROUND: Postoperative thromboprophylaxis with low molecular weight heparin (LMWH) for an extended period of 4 weeks is now preferred over short term thromboprophylaxis in patients undergoing total hip/knee arthroplasty (THA/TKA). However, most of the data demonstrating the efficacy and safety of extended thromboprophylaxis and short term thromboprophylaxis is from clinical trials done in the West. In India, the data of the incidence of venous thromboembolism (VTE) following THA/TKA has been conflicting and the duration has not been clearly defined. The aim of the study was to evaluate and compare the efficacy of extended thromboprophylaxis over short term thromboprophylaxis in Indian patients undergoing elective THA/TKA surgeries. MATERIALS AND METHODS: A prospective arm of 197 consecutive patients undergoing elective THA/TKA surgeries who were administered extended thromboprophylaxis for 4 weeks was compared with a historical group of 795 patients who were administered short term thromboprophylaxis for only 7-11 days. In both groups, LMWH (enoxaparin) was used in a dose of 40 mg subcutaneously, in addition to mechanical thromboprophylaxis. Primary efficacy endpoint was objectively confirmed venous thromboembolism (VTE). The presence of DVT was confirmed by a combination of pretest scoring, D-dimer, and Color Doppler Flow Imaging (CDFI) of deep veins of the legs, and pulmonary thromboembolism (PTE) was confirmed by ventilation perfusion (V/Q) scan or pulmonary angiography. Fisher's exact test and t test were used for the statistical analysis. The baseline confounding factors were compared between the two groups using t test for comparing the means for continuous data and Fisher's exact test for categorical data. RESULTS: In the prospective arm, only 1 patient developed symptomatic PTE compared to 26 (3.27%) cases of VTE (20 cases of PTE and 6 cases of DVT) in the retrospective group. CONCLUSION: Extended thromboprophylaxis (for 4 weeks) was found to be more effective than short term thromboprophylaxis in minimizing the risk of postoperative VTE in patients who underwent THA/TKA.

Transjugular liver biopsy.

Biopsy of the liver is considered the 'gold standard' and is often necessary for histopathological characterization of hepatic disease processes. The techniques to obtain liver specimen are percutaneous liver biopsy, transjugular liver biopsy and mini-laparoscopic liver biopsy. Percutaneous route is the preferred method for its simplicity, ease and safety. Transjugular biopsy of the liver has become an accepted alternative method of obtaining hepatic tissue in patients with an established contraindication to percutaneous liver biopsy viz. coagulopathy, ascites, extreme obesity, small shrunken liver etc. A total of 67 transjugular liver biopsies were performed between January 2004 and February 2012 in a tertiary care hospital. The procedure was performed on in patient basis after thorough pre procedure work up with jugular puncture under ultrasonography guidance and fluoroscopy guided liver biopsy using LABS 100 liver access and biopsy set. The commonest indication for liver biopsy was work up for indeterminate chronic liver disease and the most common contraindications for percutaneous biopsy that led to biopsy by transjugular route were coagulopathy and ascites. Technical success of the procedure was achieved in 96% cases and no major complications were encountered in this group. Transjugular liver biopsy is a valuable tool for clinical decision making in a specific sub set of patients in whom percutaneous biopsy is contraindicated. Transjugular approach with jugular access under real time USG guidance and liver biopsy using automated core biopsy needle is safe, well tolerated, effective and provides adequate tissue for histological assessment.