Malignant Chest Wall Tumors: Complex Defects and Their Management-A Review of 181 Cases.

BACKGROUND: Chest wall tumors are a heterogeneous group of tumors that are managed by surgeons from diverse specialties. Due to their rarity, there is no consensus on their diagnosis and management. MATERIALS: This retrospective, descriptive analysis includes patients with malignant chest wall tumors undergoing chest wall resection. Tumors were classified as primary, secondary, and metastatic tumors. The analysis includes clinicopathological characteristics, resection-reconstruction profile, and relapse patterns. RESULTS: A total of 181 patients underwent chest wall resection between 1999 and 2020. In primary tumors (69%), the majority were soft tissue tumors (59%). In secondary tumors, the majority were from the breast (45%) and lung (42%). Twenty-five percent of patients received neoadjuvant chemotherapy, and 98% of patients underwent R0 resection. Soft tissue, skeletal + soft tissue, and extended resections were performed in 45%, 70%, and 28% of patients, respectively. The majority of patients (60%) underwent rib resections, and a median of 3.5 ribs were resected. The mean defect size was 24 cm2. Soft tissue reconstruction was performed in 40% of patients, mostly with latissimus dorsi flaps. Rigid reconstruction was performed in 57% of patients, and 18% underwent mesh-bone cement sandwich technique reconstruction. Adjuvant radiotherapy and chemotherapy were given to 29% and 39% of patients, respectively. CONCLUSIONS: This is one of the largest single-institutional experiences on malignant chest wall tumors. The results highlight varied tumor spectra and multimodality approaches for optimal functional and survival outcomes. In limited resource setting, surgery, including reconstructive expertise, is very crucial.

Use of furosemide in preterm neonates with acute kidney injury is associated with increased mortality: results from the TINKER registry.

BACKGROUND: Diuretics are commonly used in neonatal AKI with the rationale to decrease positive fluid balance in critically sick neonates. The patterns of furosemide use vary among hospitals, which necessitates the need for a well-designed study. METHODS: The TINKER (The Indian Iconic Neonatal Kidney Educational Registry) study provides a database, spanning 14 centres across India since August 2018. Admitted neonates (≤ 28 days) receiving intravenous fluids for at least 48 h were included. Neonatal KDIGO criteria were used for the AKI diagnosis. Detailed clinical and laboratory parameters were collected, including the indications of furosemide use, detailed dosing, and the duration of furosemide use (in days). RESULTS: A total of 600 neonates with AKI were included. Furosemide was used in 8.8% of the neonates (53/600). Common indications of furosemide use were significant cardiac disease, fluid overload, oliguria, BPD, RDS, hypertension, and hyperkalemia. The odds of mortality was higher in neonates < 37 weeks gestational age with AKI who received furosemide compared to those who did not receive furosemide 3.78 [(1.60-8.94); p = 0.003; univariate analysis] and [3.30 (1.11-9.82); p = 0.03]; multivariate logistic regression]. CONCLUSIONS: In preterm neonates with AKI, mortality was independently associated with furosemide treatment. The furosemide usage rates were higher in neonates with associated co-morbidities, i.e. significant cardiac diseases or surgical interventions. Sicker babies needed more resuscitation at birth, and died early, and hence needed shorter furosemide courses. Thus, survival probability was higher in neonates treated with long furosemide courses vs. short courses.

Functional ß-mannooligosaccharides: Sources, enzymatic production and application as prebiotics.

One of the emerging non-digestible oligosaccharide prebiotics is ß-mannooligosaccharides (ß-MOS). ß-MOS are ß-mannan derived oligosaccharides, they are selectively fermented by gut microbiota, promoting the growth of beneficial microorganisms (probiotics), whereas the growth of enteric pathogens remains unaffected or gets inhibited in their presence, along with production of metabolites such as short-chain fatty acids. ß-MOS also exhibit several other bioactive properties and health-promoting effects. Production of ß-MOS using the enzymes such as ß-mannanases is the most effective and eco-friendly approach. For the application of ß-MOS on a large scale, their production needs to be standardized using low-cost substrates, efficient enzymes and optimization of the production conditions. Moreover, for their application, detailed in-vivo and clinical studies are required. For this, a thorough information of various studies in this regard is needed. The current review provides a comprehensive account of the enzymatic production of ß-MOS along with an evaluation of their prebiotic and other bioactive properties. Their characterization, structural-functional relationship and in-vivo studies have also been summarized. Research gaps and future prospects have also been discussed, which will help in conducting further research for the commercialization of ß-MOS as prebiotics, functional food ingredients and therapeutic agents.

Microaerobic conditions enhance laccase production from Rheinheimera sp. in an economical medium.

Statistical optimization of aeration conditions viz. aerobic, microaerobic and anaerobic, was performed using response surface methodology (RSM) utilizing soybean meal as medium to enhance the production of laccase from Rheinheimera sp. Maximum laccase yield (18.48 × 105 U/L) was obtained under microaerobic (static) conditions sustained for 12 h in tandem with 26 h aerobically (150 rpm) grown culture, which was 17.03-fold higher than laccase production in the starting M162 medium under aerobic conditions (150 rpm). The reduction in incubation time from 72 to 38 h and utilization of cost-effective soybean meal as medium, which is easily available from local market, have provided a promising, eco-friendly method of laccase enzyme production. Enhanced expression of laccase gene under microaerobic conditions corresponded to the increased expression of fnr (fumarate nitrate reductase) gene, the oxygen sensing global regulator. The putative FNR-binding site upstream of laccase transcription initiation site was predicted to play an imperative role in Rheinheimera sp. adaptation from aerobic to microaerobic conditions and for enhanced laccase production.

Neonatal acute kidney injury risk stratification score: STARZ study.

BACKGROUND: Neonates admitted in the neonatal intensive care unit are vulnerable to acute kidney injury leading to worse outcomes. It is important to identify "at-risk" neonates for early preventive measures. METHODS: The study was a multicenter, national, prospective cohort study done in 11 centers in India. A multivariable logistic regression technique with step-wise backward elimination method was used, and a "Risk Prediction Scoring" was devised [the STARZ score]. RESULTS: The neonates with admission in the NICU within <25.5 h of birth, requirement of positive pressure ventilation in the delivery room, <28 weeks gestational age, sepsis, significant cardiac disease, urine output <1.32 ml/kg/h or serum creatinine ≥0.98 mg/dl during the first 12 h post admission, use of nephrotoxic drugs, use of furosemide, or use of inotrope had a significantly higher risk of AKI at 7 days post admission in the multivariate logistic regression model. This scoring model had a sensitivity of 92.8%, specificity of 87.4% positive predictive value of 80.5%, negative predictive value of 95.6%, and accuracy of 89.4%. CONCLUSIONS: The STARZ neonatal score serves to rapidly and quantitatively determine the risk of AKI in neonates admitted to the neonatal intensive care unit. IMPACT: The STARZ neonatal score serves to rapidly and quantitatively determine the risk of AKI in neonates admitted to the neonatal intensive care unit. These neonates with a higher risk stratification score need intense monitoring and daily kidney function assessment. With this intensification of research in the field of AKI risk stratification prediction, there is hope that we will be able to decrease morbidity and mortality associated with AKI in this population.

Validation of the STARZ neonatal acute kidney injury risk stratification score.

BACKGROUND: Neonatal acute kidney injury (AKI) is common in neonatal intensive care units (NICU) and leads to worse outcomes. Stratifying neonates into an "at risk" category allows health care providers to objectively recognize opportunities for improvements in quality of care. METHODS: The "Neonatal AKI Risk Prediction Scoring" was devised as the "STARZ [Sethi, Tibrewal, Agrawal, Raina, waZir]" Score. The STARZ score was derived from our prior multicentre study analysing risk factors for AKI in neonates admitted to the NICU. This tool includes 10 variables with a total score ranging from 0 to 100 and a cut-off score of 31.5. In the present study, the scoring model has been validated in our multicentre cohort of 744 neonates. RESULTS: In the validation cohort, this scoring model had sensitivity of 82.1%, specificity 91.7%, positive predictive value 81.2%, negative predictive value 92.2% and accuracy 88.8%. Based on the STARZ cut-off score of ≥ 31.5, an area under the receiver operating characteristic (ROC) curve was observed to be 0.932 (95% CI, 0.910-0.954; p < 0.001) signifying that the discriminative power was high. In the validation cohort, the probability of AKI was less than 20% for scores up to 32, 20-40% for scores between 33 and 36, 40-60% for scores between 37 and 43, 60-80% for scores between 44 and 49, and ≥ 80% for scores ≥ 50. CONCLUSIONS: To promote the survival of susceptible neonates, early detection and prompt interventional measures based on highly evidenced research is vital. The risk of AKI in admitted neonates can be quantitatively determined by the rapid STARZ scoring system. A higher resolution version of the Graphical abstract is available as Supplementary information.

Protease Activated Receptors: A Pathway to Boosting Mesenchymal Stromal Cell Therapeutic Efficacy in Acute Respiratory Distress Syndrome?

Acute Respiratory Distress Syndrome is the most common cause of respiratory failure among critically ill patients, and its importance has been heightened during the COVID-19 pandemic. Even with the best supportive care, the mortality rate in the most severe cases is 40-50%, and the only pharmacological agent shown to be of possible benefit has been steroids. Mesenchymal stromal cells (MSCs) have been tested in several pre-clinical models of lung injury and been found to have significant therapeutic benefit related to: (a) potent immunomodulation; (b) secretion of epithelial and endothelial growth factors; and (c) augmentation of host defense to infection. Initial translational efforts have shown signs of promise, but the results have not yielded the anticipated outcomes. One potential reason is the relatively low survival of MSCs in inflammatory conditions as shown in several studies. Therefore, strategies to boost the survival of MSCs are needed to enhance their therapeutic effect. Protease-activated receptors (PARs) may represent one such possibility as they are G-protein coupled receptors expressed by MSCs and control several facets of cell behavior. This review summarizes some of the existing literature about PARs and MSCs and presents possible future areas of investigation in order to develop potential, PAR-modified MSCs with enhanced therapeutic efficiency.

Effect of age, comorbidity and remission status on outcome of COVID-19 in patients with hematological malignancies.

BACKGROUND: There is scarcity of data on outcome of COVID-19 in patients with hematological malignancies. Primary objective of study was to analyse the 14-day and 28-day mortality. Secondary objectives were to correlate age, comorbidities and remission status with outcome. METHODS: Retrospective multicentre observational study conducted in 11 centres across India. Total 130 patients with hematological malignancies and COVID-19 were enrolled. RESULTS: Fever and cough were commonest presentation. Eleven percent patients were incidentally detected. Median age of our cohort was 49.5 years. Most of our patients had a lymphoid malignancy (n = 91). One-half patients (52%) had mild infection, while moderate and severe infections contributed to one-fourth each. Sixty seven patients (52%) needed oxygen For treatment of COVID-19 infection, half(n = 66) received antivirals. Median time to RT-PCR COVID-19 negativity was 17 days (7-49 days). Nearly three-fourth (n = 95) of our patients were on anticancer treatment at time of infection, of which nearly two-third (n = 59;64%) had a delay in chemotherapy. Overall, 20% (n = 26) patients succumbed. 14-day survival and 28-day survival for whole cohort was 85.4% and 80%, respectively. One patient succumbed outside the study period on day 39. Importantly, death rate at 1 month was 50% and 60% in relapse/refractory and severe disease cohorts, respectively. Elderly patients(age ≥ 60) (p = 0.009), and severe COVID-19 infection (p = 0.000) had a poor 14-day survival. The 28-day survival was significantly better for patients in remission (p = 0.04), non-severe infection (p = 0.00), and age < 60 years (p = 0.05). CONCLUSIONS: Elderly patients with hematological malignancy and severe covid-19 have worst outcomes specially when disease is not in remission.

A missing kidney and a hidden congenital diaphragmatic hernia.

Congenital intrathoracic kidney (ITK) is a rare condition, which is usually discovered incidentally in asymptomatic children who do not need any intervention. However, it may be associated with congenital diaphragmatic hernia (CDH), in which case it requires urgent surgical intervention. We present a case of prenatally diagnosed ITK associated with a left CDH that was operated on day 5 of life. The neonate is currently well at 15 months of age.

Rice straw biochar application to soil irrigated with saline water in a cotton-wheat system improves crop performance and soil functionality in north-west India.

Applications of biochar to degraded soils have attracted considerable interest because of its capacity to enhance nutrients availability to the plants, sequester C and immobilize organic and inorganic pollutants. A five-year field experiment was conducted in a cotton-wheat system to investigate the effect of different levels of irrigation water salinity (0.3, 5, 10, and 15 dS m-1) and rice straw biochar (0, 2, 4, and 8 t ha-1) on the crop yield and soil functions. Rice straw-derived biochar was applied every year to cotton and its residual effect was observed on wheat. Results of the study indicated that regular irrigation with saline water (5-15 dS m-1) reduced both seed cotton (12-44%) and wheat grain (7-27%) yield. However, application of biochar (2-8 t ha-1) to plots irrigated with saline water showed 6-23% and 13-27% greater seed cotton and wheat grain yield compared with unamended plots, respectively. Likewise, biochar application to soil irrigated with canal or saline water showed significant beneficial effects on soil pH, EC, nutrient metabolism and availability, bulk density, infiltration rate and microbial biomass carbon. Our results indicated that biochar amendment especially at the optimum rate of 4 t ha-1 effectively promoted crop performance by ameliorating soil physical, chemical, and biological properties. In the absence of any chemical amendment for alleviating salinity stress, the results of the present study established that the biochar holds promising potential as a soil amendment in ameliorating soil functions and promoting plant productivity under saline water irrigated conditions.

PAR1 biased signaling is required for activated protein C in vivo benefits in sepsis and stroke.

Activated protein C (APC) cleaves protease-activated receptor 1 (PAR1) in vitro at R46 to initiate beneficial cell signaling; however, thrombin and APC can cleave at R41. To elucidate PAR1-dependent aspects of the pharmacologic in vivo mechanisms of APC, we generated C57BL/6 mouse strains carrying QQ41 or QQ46 point mutations in PAR1 (F2r gene). Using these strains, we determined whether or not recombinant murine signaling-selective APC mutants would reduce septic death or provide neuroprotection against ischemic stroke when mice carried PAR1-homozygous mutations that prevent cleavage at either R41 or R46. Intercrossing PAR1+/R46Q mice generated expected numbers of PAR1+/+, PAR1+/R46Q, and R46Q/R46Q offspring whereas intercrossing PAR1+/R41Q mice gave decreased R41Q/R41Q homozygotes (resembling intercrossing PAR1+/PAR1-knockout mice). QQ41-PAR1 and QQ46-PAR1 brain endothelial cells showed the predicted retention or loss of cellular responses to thrombin receptor-activating peptide, thrombin, or APC for each PAR1 mutation. In sepsis studies, exogenous APC reduced mortality from 50% to 10% in Escherichia coli-induced pneumonia for wild-type (Wt) PAR1 and QQ41-PAR1 mice (P < .01) but had no benefit for QQ46-PAR1 mice. In transient distal middle cerebral artery occlusion stroke studies, exogenous APC significantly reduced infarct size, edema, and neuronal apoptosis for Wt mice and QQ41-PAR1 mice but had no detectable benefits for mice carrying QQ46-PAR1. In functional studies of forelimb-asymmetry and foot-fault tests at 24 hours after stroke induction, signaling-selective APC was beneficial for Wt and QQ41-PAR1 mice but not QQ46-PAR1 mice. These results support the concept that APC-induced, PAR1-dependent biased signaling following R46 cleavage is central to the in vivo benefits of APC.

Lignolytic and hemicellulolytic enzyme cocktail production from Bacillus tequilensis LXM 55 and its application in pulp biobleaching.

Bioprocessing of pulp requires lignolytic as well as hemicellulolytic enzymes. The present study is the first report of a cocktail of laccase (L), xylanase (X), and mannanase (M), from a single bacterium for pulp biobleaching. A novel strain Bacillus tequilensis LXM 55 produced thermo-alkali stable L + X + M. On optimization higher enzyme yield (IUml-1/fold increase) of laccase (396.35/24.16), xylanase (212.95/81.90) and mannanase (153.33/102.90) were achieved in the cocktail. Treatment of pulp with cocktail of enzymes led to 49.35% reduction in kappa number and considerable enhancement in the brightness (11.59%), whiteness (4.11%), and other pulp properties. Most importantly, no mediator system was required for the application of laccase. 40% less chlorine consumption was required to obtain the paper of the same quality as that of pulp treated without enzyme but with 100% chlorine. Therefore, this cocktail of enzymes is highly suitable for pulp biobleaching in the paper mill.

Combinatorial Biobleaching of Mixedwood Pulp with Lignolytic and Hemicellulolytic Enzymes for Paper Making.

Microbial enzymes are the safe alternatives to chemical based bleaching of pulp in paper mills. For effective biobleaching, both hemicellulolytic and lignolytic enzymes are required. This study reports laccase (L) + xylanase (X) and laccase (L) + mannanase (M) enzyme concoctions for pulp biobleaching derived from Bacillus sp. LX and Bacillus sp. LM isolated from the decaying organic matter. All enzymes were thermo-alkali-stable, hence were suitable for their application in pulp biobleaching. When a mixture of L + X/L + M was used for mixedwood pulp biobleaching, 46.32/40.25% reduction in kappa number; 13.21/10.01% and 3.36/2.76% improvement in brightness and whiteness was achieved respectively. Moreover, no laccase mediator system was required in the current process. Significant changes in the structure of enzymatically treated pulp were also observed. All these properties make these concoctions of enzymes suitable for their application in pulp and paper mill.

The missing pieces in the jigsaw and need for cohesive research amidst coronavirus infectious disease 2019 global response.

Identifying the research needs and gaps amidst this COVID-19 travelling across the countries is absolutely important for finely improving on the way we think and act. The natural history of the disease as well as viral shedding in different stages of clinical illness needs to be known which helps in triaging the patients in hospital settings. Animal and environmental interface need to be studied for defining the high-risk situations. Transmission dynamics in community or hospital and defining the laboratory criteria for the case confirmation will be most crucial. Gene sequencing and validation and, suitable use of molecular based tests such as real-time polymerase chain reaction (qRT-PCR) should be clearly evaluated for diagnosis and/ or surveillance. The movement control strategy must be defined to prevent secondary transmission in healthcare as well as in community settings. Repurposing of drug molecules is an elegant strategy to develop therapeutics in the case of pandemics quickly. Unproven practices and treatment protocols should invite critical scrutiny on the basis of ethics. Socioeconomic status of the community is also an important determinant for the compliance and sustainable public health measures.

The TLR4-PAR1 Axis Regulates Bone Marrow Mesenchymal Stromal Cell Survival and Therapeutic Capacity in Experimental Bacterial Pneumonia.

Bone marrow derived mesenchymal stromal cells have been shown to have significant therapeutic effects in experimental models of pneumonia and lung injury. The current study examined the roles of the toll like receptor 4 (TLR4) and protease activated receptor 1 (PAR1) pathways on mesenchymal stromal cell (MSC) survival and therapeutic activity in a murine model of pneumonia. MSCs from TLR4 -/- and R41Q-PAR1 mutated mice were isolated to test the effect of mutating these specific pathways on MSC survival when exposed to cytotoxic stimuli in vitro. An Escherichia coli pneumonia model was used to assess the effect of these specific pathways on MSC therapeutic activity in vivo. Our results showed that mutation of either the TLR4 or PAR1 pathways in MSCs impaired cell survival under conditions of inflammatory stress in vitro, and eliminated their therapeutic efficacy in vivo. Also, stimulation of the TLR4 pathway on MSCs led to secretion of low levels of prothrombin by MSCs, while disrupting the TLR4 pathway impaired canonical signaling through PAR1 in response to thrombin. Therefore, this study demonstrates that both TLR4 and PAR1 are required for MSC survival under inflammatory conditions in vitro and therapeutic capacity in vivo, and that the TLR4 pathway regulates signaling through PAR1 on MSCs. Stem Cells 2018;36:796-806.

Serovar diversity of Salmonella among poultry.

Background & objectives: Salmonellosis due to the consumption of contaminated poultry products is a well-known public health concern, and assessing the distribution of Salmonella serovars among poultry becomes important for better prevention and control. The objective of the present study was to assess the distribution of Salmonella serovars among poultry. Methods: The isolates received at National Salmonella and Escherichia Centre during 2011-2016 were subjected to biochemical identification, followed by serological characterization to identify the Salmonella serovars, and the data were presented to exhibit the distribution of Salmonella serovars among poultry. Results: Salmonella was found to be present in poultry in all the regions included in the study. Salmonella Typhimurium, S. Gallinarum and S. Enteritidis were the most prevalent serovars accounting for 96.2 per cent of isolates. Salmonella was identified in poultry from all major egg-producing and egg-consuming States. Other serovars which were scantly identified included S. Infantis (2.7%), S. Montevideo (0.64%), S. Newport (0.26%) and S. Pullorum (0.13%). Interpretation & conclusions: Diverse distribution of Salmonella serovars in poultry in India, with known potential to infect human population and/or other poultry flocks, requires urgent nationwide stringent control measures.

SCH79797 improves outcomes in experimental bacterial pneumonia by boosting neutrophil killing and direct antibiotic activity.

Objectives: The role of protease-activated receptor 1 (PAR1) in the pathogenesis of pneumonia and sepsis is ambiguous given the existing literature. As PAR1 is classically activated by the coagulation-based protease thrombin and leads to vascular leakage, our hypothesis was that PAR1 blockade with SCH79797 would be therapeutically beneficial in an experimental model of murine Gram-negative pneumonia. Methods: In this study, we administered SCH79797 via the intrapulmonary route 6 h after the establishment of Escherichia coli pneumonia and observed a significant improvement in survival, lung injury, bacterial clearance and inflammation. We focused on neutrophils as a potential target of the PAR1 antagonist, since they are the predominant inflammatory cell type in the infected lung. Results: Neutrophils appear to express PAR1 at low levels and the PAR1 antagonist SCH79797 enhanced neutrophil killing. Part of this effect may be explained by alterations in the generation of reactive oxygen species (ROS). SCH79797 also led to robust neutrophil extracellular trap (NET) generation and cathelicidin-related antimicrobial peptide (CRAMP) release by neutrophils. Surprisingly, SCH79797 also had a potent, direct antibiotic effect with disruption of the E. coli cell membrane. However, the newer-generation PAR1 antagonist, vorapaxar (SCH530348), had no appreciable effect on neutrophil activity or direct bacterial killing, which suggests the effects seen with SCH79797 may be PAR1 independent. Conclusions: In summary, we observed that intrapulmonary treatment with SCH79797 has significant therapeutic effects in a model of E. coli pneumonia that appear to be due, in part, to both neutrophil-stimulating and direct antibacterial effects of SCH79797.

Empagliflozin improves cardiorespiratory fitness in type 2 diabetes: translational implications.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to prevent heart failure and reduce cardiovascular death in patients with type 2 diabetes (T2DM) and cardiovascular disease (CVD). Whether or not SGLT2 inhibitors improve indices of cardiorespiratory fitness (CRF), an independent predictor of mortality in patients with CVD, remains unknown. We evaluated the effects of empagliflozin on indices of CRF in patients with T2DM. Twenty patients with T2DM received either empagliflozin 10 mg or usual care. Baseline and 3- to 6-month post-treatment measurements of CRF were evaluated using cardiopulmonary exercise testing on a cycle ergometer. Treatment with empagliflozin led to an increased peak oxygen consumption (VO2), reduction in VE/VCO2 slope, and improvement in heart rate recovery. Our results suggest that SGLT2 inhibitors may improve markers of CRF in patients with T2DM. This may help provide important clues into the mechanism of benefit of SGLT2 inhibitors in clinical trials and provide a translational framework for the ongoing large studies of SGLT2 inhibitors in the treatment of heart failure.

Insight into microbial mannosidases: a review.

Mannan is the major constituent of hemicelluloses in softwoods. Mannan hydrolyzing enzymes cleave the 1,4-ß-mannopyranosyl linkages of the hetero-1,4-ß-d-mannans to yield mannose. ß-Mannosidases are mandatory for the complete depolymerization of mannan, these are exo-acting enzymes, which acts on non-reducing end of mannooligomers and on mannobiose removing mannose residues. Some plants and actinomycetes produce mannosidases but mainly these enzymes are produced by bacteria and fungi. The majority of microorganisms produce these enzymes extracellularly and their activity is in a wide range of pH and temperature. They have found potential applications in bioethanol production, synthesis of alkyl glycosides and, as pharmaceutical agents. Comprehensive information will be helpful for the effective understanding and application of these enzymes. This manuscript is an exhaustive review of microbial mannosidases reported to date. All the aspects such as sources, production conditions, characterization, cloning and biotechnological applications are considered.