Trends of surgical-care delivery during the COVID-19 pandemic: A multi-centre study in India (IndSurg Collaboration).

Context: The COVID-19 pandemic and subsequent lockdowns adversely affected global healthcare services to varying extents. To accommodate its added burden, emergency services were affected along-with elective surgeries. Aims: To quantify and analyze the trends of essential surgeries and bellwether procedures during the waxing and waning of the pandemic, across various hospitals in India. Settings and Design: Multi-centric retrospective study. Methods and Material: A research consortium led by World Health Organization (WHO) Collaboration Center (WHOCC) for Research in Surgical Care Delivery in Low-and Middle-Income countries, India, conducted this study with 5 centers. All surgeries performed during April 2020 (Wave I), November 2020 (Recovery I), and April 2021 (Wave II) were compared with those performed in April 2019 (pre-pandemic period). Statistical Analysis Used: Microsoft Excel 2019 and SPSS Version 20. Results: The total number of surgeries reduced by 77% during Wave I, which improved to a 52% reduction in Recovery I compared to the pre-pandemic period. However, surgeries were reduced again during Wave II to 68%, but the reduction was less compared to Wave I. Emergency and essential surgeries were affected along with the elective ones but to a lesser extent. Conclusions: The present study has quantified the effects of the pandemic on surgical-care delivery across a timeline and documented a reduction in overall surgical volumes during the peaks of the pandemic (Wave I and II) with minimal improvement as the surge of COVID-19 cases declined (Recovery II). The surgical volumes improved during the second wave compared to the first one which may be attributable to better preparedness. Cesarean sections were affected the least.

First report of Fusarium poae Causing Fusarium head Blight of Wheat in India.

Wheat is one of major cereal crops with paramount importance that is cultivated across the globe. Fusarium head blight (FHB) is a catastrophic disease of wheat which has recently risen to prominence due to its direct impact on the quality and quantity of wheat on a global scale. During a field survey conducted in Rabi 2021-22, wheat spikes showing characteristic symptoms of head blight were observed in northern parts of the Karnataka, India, in the districts Bagalkote, Belagavi and Dharwad. The infected spikelets from the heads with symptoms of infection were washed well in distilled water and surface sterilized using 1% sodium hypochlorite solution. They were further washed using sterilized distilled water to remove the traces of sodium hypochlorite. These spikelets were then transferred to sterile potato dextrose agar (PDA) plates under aseptic conditions. The plates were incubated at a temperature of 27±1°C for ten days to obtain good fungal growth. The fungus produced white to orangish pink, dense mycelia and hyaline septate hyphae. Macroconidia were sickle-shaped measuring 35.7 to 52.6 x 3.2 to 5.1 µm, dorsoventrally curved with an elongated basal cell ending in a prominent long foot; the apical cell was also elongated, tapered, slightly curved. Spores had 3 to 4 cells and formed on monophialide. Microconidia and chlamydospores were present only in a few isolates. Fungal genomic DNA was extracted from all the established isolates using CTAB (Cetyl-trimethyl ammonium bromide) method (Murray and Thompson, 1980). The ITS region of r-DNA and translation elongation factor-1 alpha (TEF-1α) genes of the ten isolates were amplified using ITS1/ITS4 primer pair (White et al. 1990) and the species-specific EF1F/EF1R primer pair (O'Donnell et al., 1998) respectively, to detect and distinguish within Fusarium species. The results exhibited 95% similarity with Fusarium poae with GenBank Accession No. XMO44849482.1. which was previously reported as a causal agent of Fusarium head blight of wheat in Georgia, USA. The TEF1-α sequences were deposited in the GenBank and the accession numbers from OP716756 to OP716765 were obtained. For the pathogenicity test, spore suspension containing a load of 108 conidia ml-1 was prepared from ten days old Fusarium poae culture and sprayed on the healthy wheat heads of the susceptible variety UAS-304 during anthesis stage by using hand atomizer. Control plants were sprayed in a similar manner with sterile distilled water. In order to enhance disease development and increase the accuracy of the evaluation, humidity was maintained for 72 hours post-inoculation period by covering each spike with a plastic bag and misting at least once daily. The characteristic head blight symptoms were observed in the inoculated wheat spikes. No symptoms were noticed in the water-treated control. The plants initially showed bleaching in single spikelet after seven days of inoculation, which eventually spread to the entire spike. After fourteen days of inoculation, the spikes showed blighted appearance with pinkish or orangish mass of mycelia grown on the affected region. The pathogen was further reisolated from the infected plants and examined under the microscope. The similar morphological features as that of the originally inoculated pathogen was observed, hence fulfilling Koch's postulates. To our knowledge, this is the first report of Fusarium poae causing head blight of wheat in India. Keeping the current climate change scenario in view, the plausibility of this pathogen causing a major havoc in the near future must not be ignored, considering the fact that it has a wide host range and highly evolving nature. The ubiquity of the Fusarium head blight recently in northern parts of Karnataka urges the need to conduct further studies on the variability, distribution and management of the pathogen.

Pharmacokinetics and tissue distribution of florfenicol and florfenicol amine in snubnose pompano (Trachinotus blochii) following oral administration.

The present study reports the comparative pharmacokinetic profiles of florfenicol and its metabolite (florfenicol amine, FFA) in Trachinotus blochii under tropical marine conditions (salinity: 35 ± 1.4‰; temperature: 28.8 ± 0.54 °C) following a single in-feed oral administration of the recommended dose (15 mg/Kg). Furthermore, the study investigated the distribution of these two compounds in nine different tissues. The maximum florfenicol concentrations (Cmax) in plasma and tissues were observed within five hours (Tmax), except for bile. The Cmax ranged from 572 to 1954 ng/g or ml and was in the intestine > bile > muscle + skin > liver > gill = heart > plasma > kidney = spleen. The elimination half-life of FFC was significantly slower in the bile (38.25 ± 4.46 h). The AUC tissue/plasma was highest for bile (3.77 ± 0.22), followed by intestine > muscle + skin > heart > liver > kidney = gill = spleen. Tmax and t1/2ß were slower, and Cmax was lower for FFA than florfenicol in all tissues except Cmax of the kidney and bile. FFA t1/2ß was exceptionally slower in the kidney (46.01 ± 8.2 h). Interestingly, reaching an apparent distribution rate of > 0.5 was comparatively faster in the kidney, liver, and gills than in other tissues. The highest apparent metabolic rate was in the kidney (0.95 ± 0.01) and the lowest in plasma (0.41 ± 0.01). The generated data can be applied for formulating efficient therapeutic protocols in T. blochii, a promising mariculture species.

Study of Serum Magnesium Levels in Patients Admitted with Sepsis in Intensive Care Unit.

Background Magnesium plays an important role in sepsis, and this could be attributed to its effects on the immune system, which are important in the pathogenesis of sepsis. Magnesium deficiency, one of the underrated electrolyte abnormalities, is observed in critically ill patients admitted to intensive care unit (ICU). Objective To find the association of serum magnesium with the outcome, duration, and need for ventilation. Method The hospital-based prospective observational study included patients > 18 years (N=150) with sepsis admitted to intensive care unit. Patients were divided into normomagnesemia (n=75) and hypomagnesemia (n=75) groups. Sequential Organ Failure Assessment Score (SOFA) score, length of intensive care unit stay, need and duration of mechanical ventilatory requirement, and outcomes were compared between the two groups. Result The mean Sequential Organ Failure Assessment score (5.87 ± 2.31 vs. 3.85 ± 1.75), mean duration of intensive care unit stay (in days) (7.21 ± 1.74 vs. 5.24 ± 1.38), the mean duration of mechanical ventilatory requirement (in days) (4.05 ± 3.47 vs. 1.13 ± 1.98), and mortality rate were (33% vs. 4%) were higher in the hypomagnesemia group when compared to the normomagnesemia group (p < 0.001 for all). Conclusion The study concludes that hypomagnesaemia is a significant electrolyte abnormality in critically ill sepsis patients. Hypomagnesaemia, Sequential Organ Failure Assessment Score, and mechanical ventilation are the factors that independently predicted mortality in intensive care unit patients. Hence, clinicians should regularly monitor the occurrence of hypomagnesemia in intensive care unit patients to reduce its poor clinical outcomes.

Microbial community composition associated with early developmental stages of the Indian white shrimp, Penaeus indicus.

Gut microbiota is known to influence the physiology, health, nutrient absorption, reproduction, and other metabolic activities of aquatic organisms. Microbial composition can influence intestinal immunity and are considered as health indicators. Information on gut microbial composition provides potential application possibilities to improve shrimp health and production. In the absence of such information for Penaeus indicus, the present study reports the microbial community structure associated with its early developmental stages. Bacterial community associated with the early developmental stages (egg, nauplii, zoea, mysis, PL1, PL6 and PL12) from two hatchery cycles were analysed employing 16S rRNA high throughput sequencing. Proteobacteria and Bacteroidetes, were the two dominant phyla in P. indicus development stages. Sequential sampling revealed the constant change in the bacterial composition at genus level. Alteromonas was dominant in egg and nauplii stage, whilst Ascidiaceihabitans (formerly Roseobacter) was the dominant genera in both PL6 and PL12. The bacterial composition was highly dynamic in early stages and our study suggests that the mysis stage is the critical phase in transforming the microbial composition and it gets stabilised by early post larval stages. This is the first report on the composition of microbiota in early developmental stages of P. indicus. Based on these results the formation of microbial composition seems to be influenced by feeding at early stages. The study provides valuable information to device intervention strategies for healthy seed production.

Abundance, community structure and diversity of nitrifying bacterial enrichments from low and high saline brackishwater environments.

The study reports diversity in nitrifying microbial enrichments from low (0·5-5‰) and high (18-35‰) saline ecosystems. Microbial community profiling of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) enrichments was analysed by sequencing 16S rRNA and was processed using Mothur pipeline. The α-diversity indices showed the richness of nitrifying bacterial consortia from the high saline environment and were clustering based on the source of the sample. AOB and NOB enrichments from both the environments showed diverse lineages of phyla distributed in both groups with 38 and 34 phyla from low saline and 53 and 40 phyla in high saline sources, respectively. At class level, α- and γ-proteobacteria were found to be more dominant in both the enrichments. AOBs and NOBs in enrichments from low saline environments were dominated by Nitrosomonadaceae, Gallionellaceae (Nitrotoga sp.) and Ectothiorhodospiraceae and Nitrospira, respectively. Though Chromatiaceae were present in both AOB and NOB enrichments, Nitrosoglobus and Nitrosococcus dominated the AOBs while NOBs were dominated by uncultured genera, whereas Rhizobiales were found in both the enrichments. AOBs and NOBs in enrichments from high saline environments were dominated by Nitrospira-like AOBs, Nitrosomonas and Nitrosococcus genera, whereas ammonia-oxidizing archaea (AOA) group included Nitrosopumilus and Nitrososphaera genera comprising and Nitrospirae, respectively. The majority of the genera obtained in both the salinities were found to be either uncultured or unclassified groups. Results of the study suggest that the AOB and NOB consortia have unique and diverse microbes in each of the enrichments, capable of functioning in aquaculture systems practised at different salinities (0-60 ppt).

Prospective impact of Corona virus disease (COVID-19) related lockdown on shrimp aquaculture sector in India - a sectoral assessment.

The lockdown on account of the Coronavirus disease 2019 (COVID-19) adversely impacted the food production sector including aquaculture, globally. Unfortunately, it coincided with the major shrimp farming season in India which contributes 60% of the national annual shrimp production hence the impact was substantial. An on-line survey was carried out among the stakeholders of the shrimp farming sector to evaluate the prospective impact of COVID-19 related lockdown across the shrimp supply chain. The study estimated an economic loss of 1.50 billion USD to the shrimp aquaculture sector during the current year. It is expected that shrimp production and its export performance may be declining by 40% in the current season. The Garret ranking and Rank Based Quotient analyses projected severe constraints in shrimp seed production and supply, disruptions in the supply chain, logistics, farming, processing, marketing and loss of employment and income for the workers due to the pandemic. To mitigate the impact, the Government of India declared fisheries and aquaculture as an essential activity, facilitated the movement of inputs and services. Further, a major Fisheries Development Scheme(PMMSY) with a financial outlay of 267 million USD has been announced to usher in a blue revolution by strengthening the value chain, doubling the fisher/farmer income, employment generation, economic and social security for fishers/fish farmers adhering to the sustainability principles. Short and medium-term technical and policy measures are suggested to tide over the impact of COVID-19 related lockdown and related restrictions.

Carbon dots: A novel trend in pharmaceutical applications.

Carbon quantum dots (CQDs, C-dots, or CDs), are generally small carbon nanoparticles having a size less than 10nm. Carbon dots (CDs) were accidentally discovered during the purification of single-walled carbon nanotubes through preparative electrophoresis in 2004. Carbon is an organic material having poor water solubility that emits less fluorescence. However, CDs have good aqueous solubility and excellent fluorescent property, hence more attention has been given to the synthesis of CDs and their applications in chemistry and allied sciences. CDs being easily accessible for in-house synthesis, simpler fabrication as per compendial requirements are wisely accepted. In addition, since CDs are biocompatible, of low toxicity, and of biodegradable nature, they appear as a promising tool for the health care sector. Furthermore, owing to their capabilities of expressing significant interaction with biological materials, and their excellent photoluminescence (PL), CDs have been emerging as novel pioneered nanoparticles useful for pharmaceutical and theranostic applications. Also, CDs are more eco-friendly in synthesis and therefore can be favorably consumed as alternatives in the further development of biological, environmental, and food areas. A massive study has been performed dealing with different approaches which are adopted for CDs synthesis and their applications as, filters for the separation of pollutants from polluted water, food safety, toxicological studies, and optical properties, etc. While still less emphasis is given on the applications of CDs in pharmaceuticals like for sustained and targeted drug delivery systems, theranostic study, etc. Hence, in the present review, we are exploring CQDs as a boon to pharmaceutical concerns.

T cell functionality in HIV-1, HIV-2 and dually infected individuals: correlates of disease progression and immune restoration.

The role of suppressive anti-retroviral therapy (ART) in eliciting restoration of dysregulated immune function remains unclear in HIV-1 infection. Also, due to tailoring of therapeutic regimens towards HIV-1, this possible impairment of therapy may be even more pronounced in HIV-2 and dual (HIV-D) infection. Thus, we evaluated the impact of ART on immune restoration by assessing T cell functions, including HIV specific responses in HIV-1-, HIV-2- and HIV-D-infected individuals. Both ART-treated and naive infected subjects showed persistently altered frequency of CD4+ T cell subsets [regulatory T cells (Treg ), naive/central memory, effector memory], increased immune activation, cytoxicity and decreased frequency of natural killer T (NKT)- like cells and T helper type 17 (Th17)/Treg ratio with elevated microbial translocation. Further, HIV-specific responses were dominated by gag-specific CD4+ T cells in virologically suppressed HIV-D individuals, suggesting retention of T cell memory for both viruses. Increased antigen-specific responses, including dual-functional interleukin (IL)-2/interferon (IFN)-γ CD4+ T cells, were detected in therapy receiving HIV-2-infected individuals indicative of a greater and more functionally diverse T cell memory repertoire. We delineated immune signatures specific to therapy-naive single HIV infection, as well as a unique signature associated with HIV-2 disease progression and immune restoration. Circulating Treg frequency, T cell activation and microbial translocation levels correlated with disease progression and immune restoration among all types of HIV infection. Also, memory responses negatively correlated, irrespective of type of infection, in ART receiving infected individuals, with CD4 rebound and decreased pan T cell activation. Our data highlight the need for adjunct immunomodulatory therapeutic strategies to achieve optimal immune restoration in HIV infection.

Watson for Oncology and breast cancer treatment recommendations: agreement with an expert multidisciplinary tumor board.

Background: Breast cancer oncologists are challenged to personalize care with rapidly changing scientific evidence, drug approvals, and treatment guidelines. Artificial intelligence (AI) clinical decision-support systems (CDSSs) have the potential to help address this challenge. We report here the results of examining the level of agreement (concordance) between treatment recommendations made by the AI CDSS Watson for Oncology (WFO) and a multidisciplinary tumor board for breast cancer. Patients and methods: Treatment recommendations were provided for 638 breast cancers between 2014 and 2016 at the Manipal Comprehensive Cancer Center, Bengaluru, India. WFO provided treatment recommendations for the identical cases in 2016. A blinded second review was carried out by the center's tumor board in 2016 for all cases in which there was not agreement, to account for treatments and guidelines not available before 2016. Treatment recommendations were considered concordant if the tumor board recommendations were designated 'recommended' or 'for consideration' by WFO. Results: Treatment concordance between WFO and the multidisciplinary tumor board occurred in 93% of breast cancer cases. Subgroup analysis found that patients with stage I or IV disease were less likely to be concordant than patients with stage II or III disease. Increasing age was found to have a major impact on concordance. Concordance declined significantly (P ≤ 0.02; P < 0.001) in all age groups compared with patients <45 years of age, except for the age group 55-64 years. Receptor status was not found to affect concordance. Conclusion: Treatment recommendations made by WFO and the tumor board were highly concordant for breast cancer cases examined. Breast cancer stage and patient age had significant influence on concordance, while receptor status alone did not. This study demonstrates that the AI clinical decision-support system WFO may be a helpful tool for breast cancer treatment decision making, especially at centers where expert breast cancer resources are limited.

Age-dependent changes in intervertebral disc cell mitochondria and bioenergetics.

Robust cellular bioenergetics is vital in the energy-demanding process of maintaining matrix homeostasis in the intervertebral disc. Age-related decline in disc cellular bioenergetics is hypothesised to contribute to the matrix homeostatic perturbation observed in intervertebral disc degeneration. The present study aimed to measure how ageing impacted disc cell mitochondria and bioenergetics. Age-related changes measured included matrix content and cellularity in disc tissue, as well as matrix synthesis, cell proliferation and senescence markers in cell cultures derived from annulus fibrosus (AF) and nucleus pulposus (NP) isolated from the discs of young (6-9 months) and older (36-50 months) New Zealand White rabbits. Cellular bioenergetic parameters were measured using a Seahorse XFe96 Analyzer, in addition to quantitating mitochondrial morphological changes and membrane potential. Ageing reduced mitochondrial number and membrane potential in both cell types. Also, it significantly reduced glycolytic capacity, mitochondrial reserve capacity, maximum aerobic capacity and non-glucose-dependent respiration in NP. Moreover, NP cells exhibited age-related decline in matrix synthesis and reduced cellularity in older tissues. Despite a lack of changes in mitochondrial respiration with age, AF cells showed an increase in glycolysis and altered matrix production. While previous studies report age-related matrix degenerative changes in disc cells, the present study revealed, for the first time, that ageing affected mitochondrial number and function, particularly in NP cells. Consequently, age-related bioenergetic changes may contribute to the functional alterations in aged NP cells that underlie disc degeneration.

Epidemiology and genetic diversity of human parechoviruses circulating among children hospitalised with acute gastroenteritis in Pune, Western India: a 5-years study.

Human parechoviruses (HPeVs) are known to cause various clinical manifestations including acute gastroenteritis. Although HPeV infections and their genotypes have been detected in human patients worldwide, no such reports are available from India to ascertain the association of HPeVs in acute gastroenteritis. The present study was conducted to determine the clinical features and genetic diversity of HPeVs detected in children hospitalised for acute gastroenteritis. Stool specimens (n = 979) collected from children aged ⩽5 years hospitalised for acute gastroenteritis in Pune, western India during January 2006-December 2010 were included. HPeV RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) (5'UTR) followed by genotyping using VP1 gene-based PCR and phylogenetic analysis. HPeV was detected in 13·9% (136/979) of the cases, co-infections with other enteric viruses were found in 43·4%. HPeV was more frequent in children ⩽1 year age with infections reported throughout the year. A total of 102/136 (75%) HPeV strains were genotyped, which comprised 13 different HPeV genotypes. Of these, HPeV1 was the most predominant genotype detected and phylogenetically clustered with the Harris strain which is rarely reported. The study documents circulation of heterogeneous HPeV genotypes. Two variant strains of HPeV4 and 'RGD absent' HPeV5 and 6 strains were also detected. This is the first report of HPeV with diversified genotypes identified in acute gastroenteritis patients from India.

Mimicking the Synaptic Weights and Human Forgetting Curve Using Hydrothermally Grown Nanostructured CuO Memristor Device.

In the present investigation, we have fabricated copper oxide (CuO) thin film memristor by employing a hydrothermal method for neuromorphic application. The X-ray diffraction pattern confirms the films are polycrystalline in nature with the monoclinic crystal structure. The developed devices show analog memory and synaptic property similar to biological neuron. The size dependent synaptic behavior is investigated for as-prepared and annealed CuO memristor. The results suggested that the magnitude of synaptic weights and resistive switching voltages are dependent on the thickness of the active layer. Synaptic weights are improved in the case of the as-prepared device whereas they are inferior for annealed CuO memristor. The rectifying property similar to a biological neuron is observed only for the as-prepared device, which suggested that as-prepared devices have better computational and learning capabilities than annealed CuO memristor. Moreover, the retention loss of the CuO memristor is in good agreement with the forgetting curve of human memory. The results suggested that hydrothermally grown CuO thin film memristor is a potential candidate for the neuromorphic device development.

Effect of orally administered vibrio bacterin on immunity, survival and growth in tiger shrimp (Penaeus monodon) grow-out culture ponds.

Vibriosis is one of the important diseases causing economic loss to the shrimp industry worldwide. The present study reports field observations on the immune stimulatory effect of vibrio bacterin in commercial tiger shrimp (Penaeus monodon) grow-out culture ponds (n = 62) which were grouped under three stocking densities; low (6-8 nos per m2 ), medium (9-11 nos per m2 ) and high (12-14 nos per m2 ). The bacterin was administered in feed as a top dressing at final concentration equivalent to 2 × 108 CFU per kilogram feed twice a week throughout the culture period. In 20 representative ponds, total haemocyte count and prophenoloxidase activity in shrimp were significantly (P < 0·05) higher and anatomical deformities like, antennae cut (5·02 ± 2·42), tail rot (5·10 ± 1·74), rostrum cut (4·49 ± 2·19) and soft shell (10·05 ± 5·77) were significantly lower compared to controls in all the studied stocking densities. Significant (P < 0·05) improvement in production parameters like survival and production (kg ha1 ) was observed in all treatment ponds while similar improvement in average daily gain and feed conversion ratio could be observed in groups with low and medium stocking densities. Results of the study suggest that, oral administration of vibrio bacterin improves the immunity, reduces anatomical deformities and enhances the production in commercial shrimp culture operations. SIGNIFICANCE AND IMPACT OF THE STUDY: Administration of vibrio bacterin in feed as a top dressing induced immune stimulation as indicated by higher levels of total haemocyte count and prophenoloxidase. Further reduction in percentage of animals with anatomical deformities suggests the protection against subclinical bacterial infections. The overall improvement in the production parameters like, average daily gain, survival, feed conversation ratio and production in different shrimp stocking densities under commercial farming conditions suggested the possible development of an immune stimulant product based on the inactivated vibrio bacteria for improved health and production in Penaeus monodon shrimp farming.

Pathogen-induced secretory diarrhea and its prevention.

Secretory diarrhea is a historically known serious health implication around the world which primarily originates through pathogenic microorganisms rather than immunological or genetical disorders. This review highlights infective mechanisms of non-inflammatory secretory diarrhea causing pathogens, known therapeutics and their efficacy against them. These non-inflammatory diarrheal pathogens breach cell barriers, induce inflammation, disrupt fluid secretion across the epithelium by alteration in ion transport by faulting cystic fibrosis transmembrane conductance regulator (CFTR), calcium activated chloride channels and ion exchanger functions. Currently, a variety of prevention strategies have been used to treat these symptoms like use of antibacterial drugs, vaccines, fluid and nutritional therapy, probiotics and prebiotics as adjuncts. In progression of the need for a therapy having quick physiological effects, withdrawing the symptoms with a wide and safe therapeutic index, newer antisecretory agents like potent inhibitors, agonists and herbal remedies are some of the interventions which have come into light through greater understanding of the mechanisms and molecular targets involved in intestinal fluid secretion. Although these therapies have their own pros and cons inside the host, the quest for new antisecretory agents has been a successful elucidation to reduce burden of diarrheal disease.

High nodal positivity rates even in good clinical responders after chemoradiation of rectal cancer: is organ preservation feasible?

AIM: Local excision (LE) is emerging as a treatment option for rectal cancer responding well to chemoradiation. However, it does not address the mesorectal nodal burden. We aimed to identify the factors influencing nodal positivity and subsequently defined a low-risk group by including only patients at low risk. METHOD: A single-centre, retrospective database analysis was carried out of patients with radically resected rectal cancer after neoadjuvant chemoradiation. RESULTS: This study included 524 patients with predominantly low rectal tumours. Nodal positivity among ypT0, T1 and T2 groups was 14.7%, 28% and 30%, respectively. Multivariate analysis with stepwise logistic regression identified the following low-risk features: age ≥ 40 years, nonsignet ring cell carcinoma (SRCC) histology and pathological complete response (pCR). Sixty-nine patients fulfilling all three criteria were analysed and the nodal positivity was found to be 10.1%, which implies that, if these patients had been selected for LE, one in 10 would have had positive mesorectal nodes. CONCLUSION: Even in patients with low-risk criteria (pCR, non-SRCC histology and age ≥ 40 years), the residual positive nodal disease burden is 10%. Whether this high incidence of residual nodal disease translates into a similar risk of locoregional recurrence if an organ-preservation strategy is adopted is unclear.

Fast track pathway reduces sight loss in giant cell arteritis: results of a longitudinal observational cohort study.

OBJECTIVES: To investigate the effectiveness of a fast track pathway (FTP) on sight loss in patients with suspected giant cell arteritis (GCA). METHODS: A longitudinal observational cohort study was conducted in the secondary care rheumatology department. One hundred and thirty-five newly referred suspected GCA patients seen via the FTP (Jan. 2012-Dec. 2013) were compared to 81 patients seen through the conventional referral and review system (Jan. 2009-Dec. 2011). RESULTS: The FTP resulted in significant reduction in irreversible sight loss from 37.0% (as seen in the historical cohort 2009-2011) to 9.0 % (2012-2013, OR 0.17, p=0.001). Adjustment for clinical and demographic parameters including known risk factors for GCA associated blindness did not significantly change the primary result (OR 0.08, p=0.001). FTP resulted in a reduction of time from symptom onset to diagnosis, particularly by reduction of time from general practitioner's (GP) referral to the rheumatology review (79% of FTP patients were seen within one working day compared to 64.6 % in the conventional pathway, p=0.023). The FTP has seen a reduction in number of GP appointments. CONCLUSIONS: There was a significant reduction of permanent sight loss with a fast track GCA pathway. The effect may be due to multiple factors including better GP education and reduction in delayed diagnosis. These results need verification at other sites.

Identification and characterization of intestinal lactobacilli strains capable of degrading immunotoxic peptides present in gluten.

AIM: Identify and characterize bacteria from the proximal gastrointestinal tract of pigs capable of degrading immunogenic gluten peptides. METHODS AND RESULTS: Bacteria were cultured from the small intestine of pigs fed a 20% gluten diet and from an enrichment media with the 18-mer peptide LQLQPFPQPQLPYPQPQL. Isolates were screened for the production of specialized proteolytic enzymes and the ability to degrade and remove metastable peptides from α-gliadin (16-mer and 33-mer) and ω-gliadin (17-mer), with established roles in the aetiology of coeliac disease. Degradation was determined by ELISA and mass spectrometry (UHPLC-MS/MS in MRM mode), and hydrolysis fragments were characterized by LC-MS/MS. Four strains from the species Lactobacillus ruminis, Lactobacillus johnsonii, Lactobacillus amylovorus and Lactobacillus salivarius showed the highest peptide-degrading activities. Strains displayed different degradation rates and cleavage patterns that resulted in reduction but not complete removal of immunotoxic epitopes. CONCLUSIONS: We employed a unique enrichment process to select for bacteria adapted to the conditions of the proximal gastrointestinal tract with the ability to partially detoxify well-characterized peptides involved in coeliac disease. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a basis for the selection of Lactobacillus strains for probiotic applications aimed to reduce epitope-containing gluten peptides before reaching the epithelium of the small intestine of patients with coeliac disease.