Search

BACKGROUND There are limited data on the role of chemotherapy in patients with small cell lung cancer (SCLC) and poor performance status (PS). METHODS This was a retrospective analysis of a prospective observational study in patients with SCLC and PS 3 or 4. We recorded the initial therapy, symptom improvement, response rate, overall survival (OS), and the impact of various factors on OS. RESULTS From June 2010 to August 2019, we enrolled 234 patients; 185 (79%) with PS 3 and 49 (21%) PS 4. Initial therapy was best supportive care (BSC) in 49 patients (21%), standard full dose chemotherapy in 31 (13%), and attenuated chemotherapy in 154 (66%). In 89% patients treated with attenuated chemotherapy, symptom-relief occurred at a median of 3 days (IQR, 1-7). Grade 3 and higher toxicities developed in 60% patients treated with initial attenuated chemotherapy, commonly hyponatremia in 39%, neutropenia in 16%, anemia in 11%, and infection in 10%. Grade 3 and higher toxicities as a result of standard chemotherapy occurred in 89% patients treated with upfront standard full dose chemotherapy compared to 69% of patients who received initial attenuated chemotherapy with subsequent treatment escalation. Overall, there were 6 (2.6%) toxic deaths. The response rate to chemotherapy was 77%. The median OS of the patients who received any chemotherapy was significantly longer at 6 months (95% CI, 4.8-7.2) compared to 1 month (95% CI, 0.4-1.6 months) in patients who were managed with BSC, p

Background Although cough is a common and distressing symptom in patients with lung cancer, there is almost no evidence to guide treatment. Aprepitant, a centrally acting neurokinin-1 inhibitor, significantly decreased cough frequency in a pilot study. Methods Patients with advanced lung cancer and cough lasting over 2 weeks despite a cough suppressant were randomized 1:1 to aprepitant 125 mg orally on day 1 and then 80 mg orally on days 2 to 7 with physician’s choice of antitussive; or to physician’s choice of antitussive alone. Evaluation was at baseline and on days 3, 7, 9, and 12. The primary end point was subjective cough improvement on day 9, measured by the Visual Analog Scale and Manchester Cough in Lung Cancer Scale. Secondary end points included quality of life (QoL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and the EORTC Lung Cancer-Specific Quality of Life Questionnaire and toxicity. Results Between 2017 and 2018, 128 patients were randomized. Median baseline cough duration was 90 days. Mean Visual Analog Scale scores (in mm) at baseline and day 9 were 68 and 39 in the aprepitant arm and 62 and 49 in the control arm, respectively (P Conclusions Aprepitant led to a significant improvement in cough in advanced lung cancer, without increasing severe side effects. Trial Registry Clinical Trials Registry-India; No.: CTRI/2017/05/008691; URL: http://ctri.nic.in

Purpose: Neurodevelopmental techniques are commonly used in upper limb rehabilitation, but little evidence supports the facilitation techniques associated with this concept. This exploratory study determined whether a facilitation technique at the triceps muscle affected scapulothoracic muscle activity during reach in healthy participants compared with self-selected posture and reach. The secondary aim was to determine whether muscle activation levels differed between the facilitation technique and the optimized posture or guided movement. We also hypothesized that activity in the scapular stabilizers (lower trapezius [LT] and serratus anterior [SA]) would be increased during the facilitated movement than in the other conditions. Methods: The study included 17 healthy participants (aged 20–70 y). Surface electromyography recorded muscle activity in the upper trapezius (UT), middle trapezius (MT), and LT muscles and in the SA, middle deltoid (MD), and triceps during five performance conditions. We used Friedman’s test to explore differences in muscle activity across conditions and Bonferroni’s post hoc test to explore the differences between conditions. Results: The facilitation technique produced decreased activity in the SA, MD, and triceps muscles ( p < 0.01) compared with the self-executed control condition. Compared with optimized posture with independent reach, facilitated movement again produced similar reductions in MD and triceps activity, with decreased LT activity also noted ( p < 0.01). Lower activity levels were noted during facilitation than during manual guidance, with or without optimized posture, in the UT, MT, ( p < 0.01), SA, and MD muscles ( p < 0.05). Conclusions: Triceps facilitation did not increase scapular stability activity, but the activity levels in several other muscle groups (SA, MD, and triceps) were reduced during triceps facilitation compared with optimized posture or guided movement. Detailed analysis of this technique, including co-registered kinematic data and timing of muscle onset, is needed.

Fluorescent nanomaterials as sensing probes have experienced immense growth in recent years due to the intrinsic optical and physicochemical properties, high sensitivity, specificity, targeting ability, and suitability for medicinal applications. The fluorescent detection of gaseous signaling molecules, such as Hydrogen sulfide (H2S), nitric oxide (NO) and carbon monoxide (CO) are very important due to their potential therapeutic application. This review intends to provide the recent progress in the detection of H2S, CO and NO via fluorescent based nano probes. These probes work based on different mechanisms such as fluorescence enhancement and quenching, also defined as "turn-on" and "turn-off" responses respectively. It could be achieved through PET, FRET or ratiometric methods. In this article, we have discussed about a variety of fluorescent nanoprobes of QDS, CDs, AuNPs and UCNPS, working on the fluorescent sensing mechanisms and applicable for the detection of H2S, CO and NO in biological and environmental samples. Methods used for the detection, structural features of nanomaterials, type of fluorescence response observed, fluorescence sensing mechanism and their sensitivity are highlighted.

The success of machine learning algorithms in medical imaging has increased the need for artificially trained models to make them work in the medical field more quickly and efficiently. This paper gives a technique to identify bone fracture using machine learning algorithms, by which workload for orthopedics can be reduced. The significant use of machine learning in this era of big medical data would help gather information from the available x-ray images rather than spending hours in the radiology departments. This paper presents imaging technologies used to identify bone fracture in the human body and give quick results once the x-ray has been taken.

On-target resistance to next-generation TRK inhibitors in TRK fusion–positive cancers is largely uncharacterized. In patients with these tumors, we found that TRK xDFG mutations confer resistance to type I next-generation TRK inhibitors designed to maintain potency against several kinase domain mutations. Computational modeling and biochemical assays showed that TRKAG667 and TRKCG696 xDFG substitutions reduce drug binding by generating steric hindrance. Concurrently, these mutations stabilize the inactive (DFG-out) conformations of the kinases, thus sensitizing these kinases to type II TRK inhibitors. Consistently, type II inhibitors impede the growth and TRK-mediated signaling of xDFG-mutant isogenic and patient-derived models. Collectively, these data demonstrate that adaptive conformational resistance can be abrogated by shifting kinase engagement modes. Given the prior identification of paralogous xDFG resistance mutations in other oncogene-addicted cancers, these findings provide insights into rational type II drug design by leveraging inhibitor class affinity switching to address recalcitrant resistant alterations. Significance: In TRK fusion–positive cancers, TRK xDFG substitutions represent a shared liability for type I TRK inhibitors. In contrast, they represent a potential biomarker of type II TRK inhibitor activity. As all currently available type II agents are multikinase inhibitors, rational drug design should focus on selective type II inhibitor creation. This article is highlighted in the In This Issue feature, p. 1

The COVID-19 pandemic has brought with it many challenges in the field of healthcare around the world. Managing burn patients has its own challenges as they require a long duration of care and are more susceptible to infection. We conducted a retrospective observational study from January 30 to July 15, 2020 at our center to study the epidemiology of burns treated & patients and healthcare workers affected by COVID-19 during this period. The number of burn admissions showed a 42.6% reduction as compared to last year. A total of 17 patients (3.67%) and 29 health care workers (8.68%) tested positive for COVID-19 in the burns department. Our strategy underwent changes based on the changing dynamics of COVID-19 and changes in government and institutional policies. We have described the various challenges we faced in managing burns during this time. We found that effective screening of patients and healthcare workers, proper segregation of negative and positive/ suspect population and a low threshold for COVID-19 testing were essential to mitigate transmission of infection.

The global pandemic COVID-19, caused by novel coronavirus SARS-CoV-2, has emerged as severe public health issue crippling world health care systems. Substantial knowledge has been generated about the pathophysiology of the disease and possible treatment modalities in a relatively short span of time. As of August 19, 2020, there is no approved drug for the treatment of COVID-19. More than 600 clinical trials for potential therapeutics are underway and the results are expected soon. Based on early experience, different treatment such as anti-viral drugs (remdesivir, favipiravir, lopinavir/ritonavir), corticosteroids (methylprednisolone, dexamethasone) or convalescent plasma therapy are recommended in addition to supportive care and symptomatic therapy. There are several treatments currently being investigated to address the pathological conditions associated with COVID-19. This review provides currently available information and insight into pathophysiology of the disease, potential targets, and relevant clinical trials for COVID-19.

Treatment of brain-related diseases is one of the most strenuous challenges in drug delivery research due to numerous hurdles, including poor blood-brain barrier penetration, lack of specificity, and severe systemic toxicities. Our research primarily focuses on the delivery of natural therapeutic compound, α-asarone, for the treatment of brain-related diseases. However, α-asarone has poor aqueous solubility, bioavailability, and stability, all of which are critical issues that need to be addressed. This study aims at formulating a lipid nanoparticulate system of α-asarone (A-LNPs) that could be used as a brain drug delivery system. The physicochemical, solid-state properties, stability, and in vitro and in vivo studies of the A-LNPs were characterized. The release of α-asarone from the A-LNPs was prolonged and sustained. After intravenous administration of A-LNPs or free α-asarone, significantly higher levels of α-asarone from the A-LNPs were detected in murine plasma and brain parenchyma fractions, confirming the ability of A-LNPs to not only maintain a therapeutic concentration of α-asarone in the plasma, but also transport α-asarone across the blood-brain barrier. These findings confirm that lipid nanoparticulate systems enable penetration of natural therapeutic compound α-asarone through the blood-brain barrier and may be a candidate for the treatment of brain-related diseases.

International audience; Purpose: Our study investigated the impact of coronary artery calcification (CAC) and systemic inflammation on risks for major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI).Background: CAC and systemic inflammation are known to be associated with an increased risk of cardiovascular events.Methods: A total of 17,711 consecutive patients who underwent PCI in our hospital between January 1, 2009 and December 31, 2015 were categorized according to the degree of CAC (moderate/severe vs. none/mild) and high-sensitivity C-reactive protein (hsCRP) level (≥2 vs.

Background Checkpoint inhibitors (Nivolumab and Pembrolizumab) are approved for multiple indications in solid tumors. However access to these therapies is limited in low and middle income countries. Hence we performed an audit to identify accessibility, adverse event rates, compliance, progression free survival and overall survival in solid tumors. Methods This was a single center retrospective analysis of prospective data base of patients with non‐melanoma solid tumors who were treated with immunotherapy from August 2015 to November 2018. Adverse events during immunotherapy were documented and graded using CTCAE (Common terminology criteria for adverse events), v. 4.02. The response rates to immunotherapy, toxicities and the time to onset and resolution of toxicities were also evaluated as secondary endpoints. Results Out of 9610 patients, only 155 patients (1.61%) could receive immunotherapy. The most common malignancies included metastatic non‐small cell lung cancer, metastatic renal cell carcinoma, metastatic urothelial carcinoma and relapsed/recurrent head and neck squamous cell carcinoma. Median overall survival in patients who received immunotherapy in non‐melanoma solid malignancies was 5.37 months (95% CI, 3.73–9.73). Poor performance status at baseline was the only adverse prognostic factor. The median progression free survival was 2.57 months (95% CI, 1.73–3.83). Immunotherapy was well tolerated with most common side effects being fatigue 14.8% and anorexia 5.8%. The cumulative incidence of immune related adverse events like hepatitis, pneumonitis, colitis and nephritis was less than 10%. Conclusion Real‐world data in Indian setting confirms the benefit of immunotherapy in patients with advanced non‐melanoma solid tumors., This is the first and largest real world data of immunotherapy from India. It focuses on efficacy and tolerability of immune check point inhibitors in Indian patients.

Patients might have teeth that are extremely mobile and/or misaligned. If multiple teeth are retained with different long axes, retrieving the impression could dislodge some of the teeth for which the long axes are inconsistent with the path of removal. In this case series, three different impression materials are used, which are low viscosity PVS (Polyvinylsiloxane), PE (Polyether) and irreversible hydrocolloid. The impression has been made to record Grade III mobile teeth. These materials quickly polymerize and do not adhere to each other intraorally. The impression is separated in three different directions to prevent any movement of the mobile teeth and reassembled extra orally before pouring. This article describes various simple and safe methods to make impressions of extremely mobile teeth. Keywords: Periodontally compromised teeth, Mobile teeth, Impression techniques, PVS (polyvinylsiloxane), PE (polyether), irreversible hydrocolloid, immediate dentures.

Background In recent times, Plasmodium vivax (P. vivax) has become a serious threat to public health due to its ability to cause severe infection with fatal outcomes. Its unique biology makes it resilient to control measures that are otherwise effective against P. falciparum. A deeper understanding of P. vivax biology and pathogenesis is, therefore, essential for developing the right control strategies. Proteomics of P. falciparum has been helpful in studying disease biology and elucidating molecular mechanisms involved in the development of disease. However, unlike P. falciparum, proteomics data for P. vivax infection is minimal due to the absence of a continuous culture system. The dependence on clinical samples and animal models has drastically limited P. vivax research, creating critical knowledge gaps in our understanding of the disease. This study describes an in-depth proteomics analysis of P. vivax-infected human plasma and parasite isolates, to understand parasite biology, pathogenesis, and to identify new diagnostic targets for P. vivax malaria. Methods A mass-spectrometry- (MS) based proteomics approach (Q Exactive) was applied to analyze human plasma and parasite isolates from vivax malaria patients visiting a primary health centre in India. Additionally, a targeted proteomics assay was standardized for validating unique peptides of most recurring parasite proteins. Results Thirty-eight P. vivax proteins were detected in human plasma with high confidence. Several glycolytic enzymes were found along with hypothetical, cytoskeletal, ribosomal, and nuclear proteins. Additionally, 103 highly abundant P. vivax proteins were detected in parasite isolates. This represents the highest number of parasite proteins to be reported from clinical samples so far. Interestingly, five of these; three Plasmodium exported proteins (PVX_003545, PVX_003555 and PVX_121935), a hypothetical protein (PVX_083555) and Pvstp1 (subtelomeric transmembrane protein 1, PVX_094303) were found in both plasma and parasite isolates. Conclusions A parasite proteomics investigation is essential to understand disease pathobiology and design novel interventions. Control strategies against P. vivax also depend on early diagnosis. This work provides deeper insights into the biology of P. vivax by identifying proteins expressed by the parasite during its complex life-cycle within the human host. The study also reports antigens that may be explored as diagnostic candidates.

Bedaquiline and delamanid used to treat extensively drug-resistant tuberculosis are known to cause prolonged QTc. Two children with extensively drug-resistant tuberculosis were put on bedaquiline and delamanid and had prolonged QTc on the Bazett formula but normal QTc by the Fridericia formula. Both had no adverse effects. Correct formula for monitoring QTc should be used thereby preventing unnecessary withholding of medicines.

Background More than 350 K described species, Coleoptera (beetles) represent the most diverse order from Class Insecta in the entire animal kingdom. However, their phylogeny is highly controversial due to their morphological crypticness and multiple markers used previously for sequence homology. Although many studies suggest that their diversity currently relies majorly on morphological analysis, nevertheless DNA barcodes may provide a functional, standardized tool for their unique identification. In the present report, a fragment of the mitochondrial cytochrome c oxidase I (COI) gene has been proposed as standard DNA barcoding marker for the identification of organisms. Result To evaluate this hypothesis, a random sampling was conducted in and around Vadodara, Gujarat, where 2690 individual of 65 species belonging to 16 families were reported from different sites, and diversity indices were employed to unravel the species composition of that habitat. Further, 12 beetles from dominant families were selected for sequence analysis using various bioinformatics tools and were compared with the rest of the beetles to obtain a more robust phylogeny which is not reported earlier in previous studies. Conclusion Hence, the present study suggests that Scarabaeidae tends to be more diverse in and nearby of Vadodara compared to all other families of Coleoptera and while in contrast Chrysomelidae showed maximum diversity of pest species. DNA barcoding and nucleotide analysis resolves the phylogeny of controversial taxa; (Adephaga(Gyrinidae+ (Dytiscidae++ Carabidae)) (Polyphaga(Histeridae+Buprestidae+Lampyridae+Elateridae+(Scarabaeidae+(Coccinelidae+ Apionidae+Curculionidae+ (Meloidae+Tenebrionidae+(Cerambycidae+Chrysomelidae)))))).

OBJECTIVES To present clinical and cytopathological features of nine cases of chordomas, diagnosed over 9 years and confirmed by brachyury (T) immunostaining. METHODS Conventional cytological smears, stained with Papanicolaou and May-Grunwald Giemsa, along with corresponding histopathological (n = 8) and immunostained sections (n = 8) were reviewed. Immunohistochemical staining was performed on tissue sections by polymer detection technique. RESULTS Nine tumours occurred in seven males and two females, with age ranging from 36 to 72 years (average = 58.7), in the sacrum (seven) and spine (two). On fine needle aspiration cytology, five cases were either diagnosed with or diagnosed with a suggestion of a chordoma, while three cases were diagnosed with chordoma as a differential diagnosis. On review, smears were moderately cellular, comprising myxoid stroma (9/9), epithelioid cells (9/9), physaliphorous cells (8/9), including binucleation (7/9), prominent nucleolisation (2/9), pleomorphic cells (2/9) and intranuclear inclusions (3/9). Immunohistochemically, tumour cells expressed cytokeratin (4/4), pan cytokeratin (4/4), epithelial membrane antigen (8/8), S100 protein (6/8) and brachyury (8/8). Five patients underwent surgical excision, including two who underwent adjuvant radiotherapy (RT) and four patients who underwent RT. During follow-up (n = 8), a single patient developed recurrence and another presented with metastatic lesions. Finally, five patients were alive with disease (7-53 months); a single patient was free of disease (4 months), and two patients died of disease; the latter cases displayed pleomorphic cells and intranuclear inclusions. CONCLUSIONS Chordomas can be primarily diagnosed by fine needle aspiration cytology in a typical clinicoradiological setting with a combination of key cytomorphological features. Pleomorphic cells and intranuclear inclusions are associated with a relatively aggressive subtype. An exact diagnosis has treatment implications and requires confirmation by brachyury immunostaining.

Protein-based therapeutics are significantly reaching the market owing to strides in genetic engineering and target specific drug design. However, majority of the products are available as parenteral and subcutaneous dosage forms. The lungs provide a noninvasive passage for systemic absorption of proteins, with advantages like large surface area (50–75 m2), milder local microenvironment and proteolytic activity as compared to the gastrointestinal tract and a permeable epithelial layer with perfuse vasculature. Even so, the proteins delivered to the lungs are subjected to some degradation via proteolytic enzymes, macrophage assisted clearance, degradation due to chemical destabilization and physical hindrances to permeation. Recent research has been targeted towards identifying these challenges and using formulation development as a tool to overcome one or several of these questions. Preparation of nano-sized and micron-sized polymeric or lipid-based protein formulations offers unmatched advantages such as sustained protein release, distribution and retention in lungs and stabilizing by shielding from local microenvironment. However, degradation of proteins while manufacturing, regulation of particle size, scale-up, long-term safety for chronic conditions (like diabetes or growth hormone deficiency) and translation from bench-to-bedside are some major challenges. Strategies for pulmonary permeation enhancement via paracellular and trans-cellular mechanisms and protein stabilization by prevention of degradation have also been evaluated. This review provides in-depth summary to identify and evaluate the potential of the pulmonary route for delivery of therapeutic proteins.

Studies have shown worse outcome for women compared with men after percutaneous coronary intervention (PCI), especially in the presence of diabetes mellitus (DM). We aimed to investigate the risk of ischemic events after PCI in women versus men stratified by the presence or absence of DM. A total of 17,154 consecutive patients from a single-center PCI registry enrolled from January 2009 to December 2014 were categorized accordingly: female/non-DM, female/DM, male/non-DM, and male/DM. End points included death and myocardial infarction (MI) at 1 year. Of the overall population, 15% (n = 2,631) were female/non-DM, 17% (n = 2,891) were female/DM, 38% (n = 6,483) were male/non-DM, and 30% (n = 5,149) were male/DM. Within the 4 study groups, female/DM had the highest risk, whereas female/non-DM and male/DM showed similar risks and male/non-DM showed lowest risk for death (4.64% vs 3.08% vs 2.93% vs 2.31%; p-trend0.0001 over all groups and p = 0.69 between female/non-DM and male/DM, respectively) and MI (4.15% vs 3.99% vs 3.71% vs 2.55%; p trend0.0001 over all groups and p = 0.97 between female/non-DM and male/DM, respectively). After multivariate adjustment findings were largely unchanged suggesting highest risk for adverse events in diabetic women compared with other groups and comparable risks for death and MI in nondiabetic women compared with diabetic men. In conclusion, these findings highlight the combined influence of DM and female gender as strong determinants of post-PCI risk while also illustrating "risk equivalence" between nondiabetic women versus diabetic men.

Acoustic Voice Quality Index (AVQI) has been reported to be a sensitive tool for discriminating between the normal and dysphonic voices, however, there is a dearth of research focused on investigating the diagnostic accuracy of AVQI in discriminating across the perceptual categories of dysphonia severity ie, slight, moderate, and severe. Hence, the present study is a preliminary attempt to document the AVQI across the degrees of dysphonia severity and to verify whether the AVQI can discriminate across these degrees of perceptual dysphonia severity.A total of 71 dysphonic samples extracted from the clinical database of the institute and 19 prospectively recorded normophonic samples consisting of sustained vowel /a/ and a sentence from a standardized Kannada passage served as input data. These 90 samples were categorized into four categories based on the overall grade of perceptual dysphonia (G) as normal, slight, moderate, or severe by three experienced speech language pathologists in a randomized and double-blinded manner, which served as the ground truth. The AVQI was calculated from the samples using Praat version 6.0.40 and the AVQI script version 2.03.The Spearman's correlation test revealed a positive correlation between the G and the AVQI (r = 0.67; P0.001). The Receiver Operating Characteristics analysis revealed that the AVQI could accurately discriminate across the perceptual subcategories of dysphonia.The results of the present study revealed that AVQI is a robust multiparametric measure which can accurately discriminate across the subcategories of the perceptual dysphonia severity with reasonable precision. Further, the AVQI is also shown to be promising in evaluating the signals with higher levels of aperiodicity such as severe hoarse voice quality.

Hot-melt extrusion (HME) has emerged as a pioneering manufacturing technology for pharmaceutical industries, and the utilization is overgrowing due to its unit operation, cost-effectiveness, solvent-free nature, and continuous manufacturing as compared to conventional techniques. Prime importance should be given to study the formulation as well as process parameters to meet requirements. By modifying the equipment design and varying a few processing conditions, a myriad of different dosage forms for various applications can be developed. In-depth pre-formulation research is required for the rational selection of an active pharmaceutical ingredient, carrier, and additives for the smooth and continuous functioning of the HME process to achieve the desired product. This review channels to a holistic perspective of several equipment components, processing requirements, materials used in HME, and various drug delivery systems utilizing HME in recent years. It gives a comprehensive treatise on several novel opportunities and innovations such as three-dimensional printed dosage forms, abuse-deterrent formulations, co-extrusion, chronotherapeutic drug delivery, co-crystals, nanotechnology, semi-solids, twin-screw granulation, and miscellaneous applications. The progress described herein may also flourish the drug delivery scenario in the veterinary clinics by employing HME technology, which is briefly discussed in this review for the first time. The article also highlights a brief insight into the global status of the pharmaceutical HME market during the period between 2016 and 2024. Lattermost, this review summarizes several applications of HME over the recent four years in drug delivery in a tabular form for ease of readers. Overall, this article is an attempt to lay a bibliographic foundation for formulator scientists working in this area and promote further investigations in this field.

Tuberculosis (TB) is one of the primary infectious diseases in the world and is accountable for more than two million deaths and nine million new cases every year. Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis that is resistant to two or more of the primary drugs (e.g. isoniazid and rifampin) used for the management of tuberculosis. The aminoglycoside group is the major drug group which is used in the treatment of patients with TB and can lead to hearing loss as they are ototoxic in nature. Here, we describe three patients with MDR-TB who were under medication for the same, i.e. aminoglycoside drug group along with few more antibacterial agents and anti-tuberculosis agents. The results of audiological evaluation suggested that all the patients considered for the study had the bilateral sensorineural hearing loss, where 2, 4 and 8 kHz were more affected compared to 250, 500 and 1 kHz. Other symptoms reported were tinnitus, episodic vertigo, decreased vision, general body ache, reduced appetite and insomnia.

There are little data on the efficacy and safety of taxane/platinum with definitive radiotherapy (RT) for esophageal/GEJ cancer. This article is a retrospective analysis of patients who received weekly paclitaxel 50 mg/m2 and carboplatin AUC 2 with radical definitive RT for locally advanced esophageal/GEJ cancer. Between February 2011 and July 2014, 179 patients were included. The median age was 54 years. Ninety-two percent of patients had squamous histology. Mean RT dose was 58.7 Gy in 32 fractions over 53 days, with mean of six chemotherapy cycles. Fifty-six percent of patients developed ≥grade 3 acute toxicities, commonly febrile neutropenia (12%) and infection (11%); ≥grade 3 laboratory abnormalities included hyponatremia (38%), leukopenia (49%), neutropenia (27%), and anemia (16%). Twelve percent of patients developed ≥grade 3 chronic toxicity. Fatal toxicities included six during CRT, eight within 30 days of completing CRT, and three chronic. Radiologic response was 49% (CR 5.6%, PR 43%). Follow-up endoscopy showed remission in 53% and residual disease in 14%. At a median follow-up of 28 months, median PFS was 11 months (95% CI: 8‐13.9), median OS was 19 months (95% CI: 15.4‐22.6), and estimated 1-year, 2-year, and 3-year survivals were 70%, 47%, and 39%, respectively. Weekly paclitaxel‐carboplatin concurrently with definitive RT is efficacious with manageable toxicity. [The trial was registered with the Clinical Trials Registry-India (CTRI), registration number: CTRI/2014/07/004776.]

Introduction Burn care was revolutionized by critical care and excision surgeries which drastically improved the survival rates of the patients. Another cornerstone and basic surgery in all these patients is the skin grafting. Traditionally skin grafts are fixed using sutures, staplers and cyanoacrylate glue. The study was conducted to compare the efficacy and effects of fibrin sealant and cyanoacrylate glue in graft fixation and scar characteristics after skin grafting in post burn raw areas. Materials and methods The study was conducted as a retrospective comparative cohort study with prospective follow-up conducted at a tertiary burn care centre in India over a period of one year which included patients between 18–50 years who presented with post burn raw areas and underwent skin graft fixation with fibrin sealant or cyanoacrylate glue. Results Data from 40 patients were collected and analyzed in the study. Group 1 (Fibrin sealant) and group 2 (Cyanoacrylate glue) included 20 patients each. The percentage of graft take at the end of 15th post-operative day was higher in group 1 in comparison to group 2 (95 % and 90.2 % respectively). Two patients had graft failure (Mean - 26.75 %) in group 1 in comparison to five in group 2 (Mean - 38.16 %). At end of six months, on modified Vancouver scar scale in categories of pigmentation, vascularity, thickness and pliability - the subjective scorings were better in group 1 overall. Histopathological and immuno-histochemical staining showed better scar characteristics in group 1. Conclusion The use of fibrin sealant has shown better results when compared to cyanoacrylate glue in the fixation of skin grafts in post burn raw areas. The superior scores in clinical and histopathological scar characteristics in fibrin sealant group may indicate the role of Fibrin sealant in scar modulation.

Mutations in the pioneer transcription factor FOXA1 are a hallmark of estrogen receptor-positive (ER(+)) breast cancers. Examining FOXA1 in ~5,000 breast cancer patients identifies several hotspot mutations in the Wing2 region and a breast cancer-specific mutation SY242CS, located in the third β strand. Using a clinico-genomically curated cohort, together with breast cancer models, we find that FOXA1 mutations associate with a lower response to aromatase inhibitors. Mechanistically, Wing2 mutations display increased chromatin binding at ER loci upon estrogen stimulation, and an enhanced ER-mediated transcription without changes in chromatin accessibility. In contrast, SY242CS shows neomorphic properties that include the ability to open distinct chromatin regions and activate an alternative cistrome and transcriptome. Structural modeling predicts that SY242CS confers a conformational change that mediates stable binding to a non-canonical DNA motif. Taken together, our results provide insights into how FOXA1 mutations perturb its function to dictate cancer progression and therapeutic response.

Last decade has seen emergence of particle shape as a critical design parameter to overcome several long standing problems associated with particulate drug delivery- non-specific drug effects, RES uptake, poor bioavailability, achieving controlled release profiles, predictable degradation profiles, longer circulation time and zero order release kinetics to name a few. Non-spherical particles have been synthesized by techniques ranging from classical solvent evaporation to specialized techniques like film stretching and PRINT®. Non-spherical particles tend to show a difference in macrophage uptake, adhesion to target cells and distribution in vivo. This review also discusses these effects and its implications. Lastly, the impact of particle aspect ratio and other shape-governed parameters on flow properties, dispersion viscosities and other pharmaceutically relevant aspects have been briefly explained. Although there are no thumb rules yet, modern and classical literature on behavior of non-spherical particles has been reviewed and the observations have been trend-lined.

Background: The objective was to study the cases of HELLP syndrome and its management and outcome in a tertiary health care system. Methods: Three Hundred Twenty patients with gestational age >20 weeks were selected whose BP recorded more than 140/90 mm Hg. This study was done from July 2014 to July 2016. Required laboratory investigations were carried out and the outcome was studied with respect to maternal and fetal outcome. Results: The association with HELLP/ Partial HELLP was not significantly associated with the parity and the family history. There was a strong association of HELLP/ Partial HELLP with Pre eclampsia and all the three tests (hemolysis, liver enzymes, platelet count) that was considered to be the gold standard tests to identify the pathology. Conclusions: The association points towards only one point, that is to identify and treat the patients immediately in order to reduce maternal and neonatal morbidity and mortality.

Aims: It remains unknown what percentage of patients treated with percutaneous coronary artery intervention (PCI) have high residual inflammatory risk (RIR). Moreover, the impact of RIR on clinical outcomes has not been established. The objective of this study is to determine the prevalence of patients with persistent high levels of inflammation after PCI and to evaluate clinical outcomes according to inflammatory response. Methods and results: This is a retrospective cohort study assessing patients undergoing PCI between 2009 and 2016 with serial inflammatory status assessment from a large, prospective, and single-centre PCI registry. Assessment of inflammation status with at least two high sensitive C-reactive protein (hsCRP) measurements at baseline and follow-up with >4 weeks apart. High RIR was defined as an hsCRP≥ 2 mg/L. Patients were divided into four groups: persistent high RIR, increased RIR (first low-, then high hsCRP), attenuated RIR (first high-, then low hsCRP), or persistent low RIR. The primary endpoint was all-cause mortality at 1 year follow-up. Occurrence of myocardial infarction (MI) was assessed as secondary outcome. Seven thousand and twenty-six patients were identified with serial hsCRP measurements (30.8% of all PCI patients). Of these patients 2654 (38%) had persistent high RIR, 719 patients (10%) had increased RIR, 1088 patients (15%) had attenuated RIR, and persistent low RIR was seen in 2565 patients (37%). All-cause mortality at 1 year was 2.6% in patients with persistent high RIR, compared with 1.0% in increased RIR, 0.3% in attenuated RIR, and 0.7% in persistent low RIR patients, P

This chapter reviews various enzymes produced by the colonic microflora and their utilization in the development of pharmaceutical dosage forms to achieve colon-specific drug delivery. This chapter discusses the applications of colonic bacterial enzymes in order to surrogate colonic conditions in vivo so as to evaluate in vitro drug release from microbially triggered/enzymatically triggered colon-specific drug delivery systems. This chapter also discusses different methods to produce colonic bacterial enzymes as well as use of probiotics as a source to produce colonic bacterial enzymes.

Summary Objectives The study aimed to investigate and compare the acoustic and aerodynamic characteristics of choral singers and nonsingers. Method Twenty choral singers and 20 nonsingers in the age range of 20–30 years with no vocal pathology participated in the study. For acoustic analysis, the voice sample was recorded and analyzed using Praat software (Phonetic Sciences, University of Amsterdam, Amsterdam, Netherlands) version 6.0.33 and for aerodynamic evaluation, Helios 401 PC based spirometer (Recorders & Medicare System Pvt. Ltd., Panchkula, Haryana, India) was used. Results The results from acoustic analysis of female groups revealed higher F0 in singers than nonsingers; higher jitter, shimmer, and noise-to-harmonics ratio (NHR) values were obtained for nonsingers compared to singers. Results from acoustic analysis of male groups revealed significantly higher F0 in singers than nonsingers and significantly higher shimmer and NHR values for nonsingers compared to singers. Results from aerodynamic analysis for both male and female groups revealed higher vital capacity, forced vital capacity, and slow vital capacity in singers than nonsingers. Conclusion The results revealed better control over phonatory and respiratory subsystems among singers compared to nonsingers, although the singers were untrained. This could be possible due to the fact that long-term singing practices involving vocal modulation and changes in the breathing pattern, better respiratory control during the expiratory phase among singers. However, as the participants of the singing group are untrained, further studies are required to compare the acoustic and the aerodynamic characteristics with trained singers.

9001 Background: Standard first-line therapy for EGFR mutant advanced non-small cell lung cancer (NSCLC) is an EGFR-directed oral TKI. We evaluated whether adding pemetrexed-carboplatin to oral TKI would improve outcomes. Methods: Phase III randomized trial in advanced chemotherapy-naïve NSCLC harboring EGFR sensitizing mutation (exon 19, 21 or 18) with performance status (PS) 0 to 2 planned for palliative therapy. Patients were stratified for PS and EGFR mutation and randomly assigned (computer-generated randomization by independent biostatistician) 1:1 to gefitinib 250 mg orally daily (gef) or gefitinib 250 mg orally daily with pemetrexed 500 mg/m2 IV and carboplatin AUC 5 IV every 3 weeks for 4 cycles, followed by maintenance pemetrexed 500 mg/m2 IV every 3 weeks (gef+C). Restaging was every 2 to 3 mths; therapy continued until progression or intolerable toxicity. Primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), toxicity and response rate. Survival endpoints were assessed in the intention-to-treat population. Results: Between Aug 2016 and Aug 2018, 350 patients were randomly assigned to gef (n = 177) and gef+C (n = 173). Median age was 54 yrs, 48% were females, 84% never-smokers, 21% were PS 2 and 18% had brain metastases. Median follow-up in surviving patients was 17 months (range, 7 to 30). Radiologic response rates were 81% and 69% in gef+C and gef respectively, P = 0.012. 234 patients (67%) have had events for PFS, 98 in gef+C and 136 in gef. Estimated median PFS was significantly longer with gef+C than gef (16 months, [95% CI, 13.7 to 18.3] vs. 8 months [95% CI, 7.1 to 8.9]; hazard ratio for disease progression or death, 0.5; 95% CI, 0.39 to 0.65; P < 0.001). 120 patients (34%) have died, 42 in gef+C and 78 in gef. Estimated median OS was significantly longer with gef+C than gef (not reached vs. 18 months [95% CI, 14.28 to 21.72]; hazard ratio for death, 0.45; 95% CI, 0.31 to 0.66; P < 0.001). Clinically relevant ≥ grade 3 toxicities occurred in 51% and 25% of patients in gef+C and gef arms respectively, P < 0.001. Conclusion: Adding pemetrexed-carboplatin chemotherapy to gefitinib significantly prolonged progression free and overall survival but also increased toxicity. Pemetrexed-carboplatin-gefitinib represents a new standard first-line therapy for EGFR mutant NSCLC. Clinical trial information: CTRI/2016/08/007149.

Objectives: To study the utility of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting (1) the World Health Organization (WHO) histologic type and differentiating low-risk from high-risk types. (2) Tumor stage and differentiate early from advanced stage disease. Materials and Methods: Patients with thymic epithelial neoplasia who underwent a pretreatment FDG-PET study were included. Tumor maximum standardized uptake value (SUVmax) was correlated with the WHO histologic type and also with the Masaoka-Koga (MK) staging system. Patients with WHO Type A, AB, and B1 were classified as low risk and those with B2 and B3 as high risk. Thymic carcinomas belonged to Type C. Patients with MK Stage I and II disease were grouped as early stage and those with Stage III and IV as an advanced stage. Differences in SUVmax between the various groups were calculated. Results: The SUVmax of thymic carcinomas was significantly higher as compared to low-risk (P = 0.001) and high-risk groups (P = 0.007). The SUVmax of high-risk group was also significantly higher than the low-risk group (P = 0.002). SUVmax cutoff of 6.5 was able to differentiate thymic carcinomas from thymomas with 100% sensitivity and 87.2% specificity. The SUVmax in patients with advanced stage disease showed a higher trend compared to those with early stage, but the difference was not significant (P = 0.167). Conclusion: PET can differentiate thymic carcinomas from rest of the thymoma subtypes by the virtue of their higher FDG uptake. It can also provide valuable information in differentiating high-risk from low-risk thymomas and in predicting disease stage.

Background: Appendicitis is notorious in its ability to simulate other conditions and accurate diagnosis is imperative for preventing complications of appendicitis on one hand and avoiding negative appendectomy on other. Despite extraordinary advances in modern radiography imaging and diagnostic laboratory investigations, the accurate diagnosis of acute appendicitis remains an enigmatic challenge.Methods: We evaluated 32 patients with features suggestive of acute appendicitis between September 2013 to March 2015. It was a cross-sectional observational study that included modified Alvarado score (MAS) and ultrasound (USG) in predicting appendicitis and correlated both these individually as well as combined, with histopathological findings. Statistical analysis was done by Chi-square test with Yates correction, Fischer’s exact test and unpaired Students’ t test.Results: Ultrasound was found to be more sensitive (74.19%) and accurate (75.0%) as compared to MAS (41.94% and 43.75% respectively). The specificity and positive predictive value (PPV) were similar in both the parameters (100% each). Also, when both the MAS and Ultrasound were combined in predicting acute appendicitis, the sensitivity, negative predictive value and accuracy increased to 80.64%, 14.29% and 81.25% respectively with specificity and PPV being the same as when MAS and USG were considered individually.Conclusions: It is advised that both modified Alvarado score and ultrasound whenever available should be used to predict acute appendicitis to increase the number of positive cases and reduce negative appendectomy and hence reduce the morbidity and mortality.

Summary Background Dysphonia is a variation in an individual's quality, pitch, or loudness from the voice characteristics typical of a speaker of similar age, gender, cultural background, and geographic location. Dysphonia Severity Index (DSI) is a recognized assessment tool based on a weighted combination of maximum phonation time, highest frequency, lowest intensity, and jitter (%) of an individual. Although dysphonia in adults is accurately evaluated using DSI, standard reference values for school-age children have not been studied. Aim This study aims to document the DSI scores in typically developing children (8–12 years). Method A total of 42 typically developing children (8–12 years) without complaint of voice problem on the day of testing participated in the study. DSI was computed by substituting the raw scores of substituent parameters: maximum phonation time, highest frequency, lowest intensity, and jitter% using various modules of CSL 4500 software. Results The average DSI values obtained in children were 2.9 (1.23) and 3.8 (1.29) for males and females, respectively. DSI values are found to be significantly higher ( P = 0.027) for females than those for males in Indian children. This could be attributed to the anatomical and behavioral differences among females and males. Further, pubertal changes set in earlier for females approximating an adult-like physiology, thereby leading to higher DSI values in them. Conclusion The mean DSI value obtained for male and female Indian children can be used as a preliminary reference data against which the DSI values of school-age children with dysphonia can be compared.

BACKGROUND: Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has become a preferred imaging modality for the evaluation of solitary pulmonary nodule (SPN), particularly in the developed world. Since FDG can concentrate in infective/inflammatory lesions, the diagnostic utility of FDG-PET can be questioned, particularly in regions endemic for infectious decisions. AIM: To evaluate the accuracy of FDG-PET/CT in evaluation of SPNs in a population endemic for infectious disease and to assess if regional variations have an impact on its effectiveness. MATERIALS AND METHODS: All patients who underwent an FDG/PET-CT with a clinico-radiological diagnosis of SPN categorized as indeterminate were included. Based on a maximum standardized uptake values (SUVmax) cut-off of 2.5, lesions were classified as benign ( 2.5) and compared with gold standard histopathology. The diagnostic accuracy of PET-CT to detect malignancy was calculated. On the basis of final histopathology, lesions were grouped as (a) malignant nodules (b) infective/granulomatous nodules with a specific diagnosis and (c) nonspecific inflammatory nodules. The SUVmaxbetween these groups was compared using nonparametric statistical tests. RESULTS: A total of 191 patients (129 males, 62 females) with a median age of 64 years (range: 36–83) were included. Totally, 144 nodules (75.3%) were malignant and 47 were benign (24.7%). Adenocarcinoma (n = 84) was the most common malignancy. Tuberculosis (n = 16) and nonspecific infections (n = 24) were the two most common benign pathologies. There was a significant overlap in the metabolic uptake of malignant (median SUVmax-11.2, range: 3.3–34.6) and tuberculous nodules (median SUVmax-10.3, range: 2.7–22.5) with no statistically difference between their SUVmaxvalues (P = 0.43). The false-positive rate was 65.2% and the false-negative rate was 5.5%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-PET/CT for detecting malignancy were 94.4%, 34.7%, 81.9%, 66.6%, and 79.5%, respectively. CONCLUSIONS: Though FDG-PET scans show a very high sensitivity for malignant nodules, it has a high false-positive rate and reduced specificity when characterizing SPNs in an infectious endemic region. Physicians must be aware of this limitation in the workup of lung nodules, and regional variations must be considered before further management decisions are taken.