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1.
J R Coll Physicians Edinb ; : 14782715241244839, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38576167

ABSTRACT

A 49-year-old female patient presented at the hospital with a history of herpetic blisters, frequent episodes of vomiting and loose stools, bilateral upper and lower limb weakness, and diminishing sensorium. She was diagnosed with hyponatraemia and respiratory failure and later became unconscious with absent brainstem reflexes. The patient was initially treated for herpetic encephalitis, a chronic obstructive pulmonary disease with acute exacerbation, hyponatraemia and neuroparalytic snake bite. Further evaluation, however, identified the uncommon Guillain Barre syndrome presentation with overlap of Bickerstaff brainstem encephalitis. This is an uncommon disorder characterised by the involvement of higher mental functions, fixed dilated pupils, absent brainstem reflexes and quadriplegia that resembles a neuroparalytic snake bite and brain death. After receiving intravenous immunoglobulins for treatment, the patient completely recovered.

3.
Ann Surg ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38606560

ABSTRACT

BACKGROUND: In the last two decades the development of high-resolution manometry (HRM) has changed and revolutionized the diagnostic assessment of patients complain foregut symptoms. The role of HRM before and after antireflux procedure remains unclear, especially in surgical practice, where a clear understanding of esophageal physiology and hiatus anatomy is essential for optimal outcome of antireflux surgery (ARS). Surgeons and gastroenterologists (GIs) agree that assessing patients following antireflux procedures can be challenging. Although endoscopy and barium-swallow can reveal anatomic abnormalities, physiologic information on HRM allowing insight into the cause of eventually recurrent symptoms could be key to clinical decision making. METHOD: A multi-disciplinary international working group (14 surgeons and 15 GIs) collaborated to develop consensus on the role of HRM pre- and post- ARS, and to develop a postoperative classification to interpret HRM findings. The method utilized was detailed literature review to develop statements, and the RAND/University of California, Los Angeles Appropriateness Methodology (RAM) to assess agreement with the statements. Only statements with an approval rate >80% or a final ranking with a median score of 7 were accepted in the consensus. The working groups evaluated the role of HRM prior to ARS and the role of HRM following ARS. CONCLUSION: This international initiative developed by surgeons and GIs together, summarizes the state of our knowledge of the use of HRM pre- and post-ARS. The Padova Classification was developed to facilitate the interpretation of HRM studies of patients underwent ARS.

4.
Lung India ; 41(3): 176-180, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38687227

ABSTRACT

BACKGROUND: Mechanical ventilation is essential for managing acute respiratory failure, but traditional methods of assessing oxygenation, like the PaO2/FiO2 ratio, pose challenges due to invasiveness and cost. OBJECTIVE: This single-centre prospective observational study aimed to assess the potential of the non-invasive Oxygen Saturation Index (OSI), utilising SpO2 measurements, to diagnose hypoxemia in mechanically ventilated adults. The study sought to establish correlations between OSI, oxygenation index (OI), PaO2/FiO2 ratio and SpO2/FiO2 ratio. METHODS: From August 2022 to July 2023, data was collected from 1055 mechanically ventilated intensive care unit patients. Statistical analysis included correlation tests, receiver operating curve (ROC) analysis and cut-off value determination for hypoxemia diagnosis. RESULTS: We found that the P/F ratio had a statistically significant negative correlation with OI (correlation coefficient -0.832, P value: 0.000 in hypoxemic group and correlation coefficient -0.888, P value: 0.000 in the non-hypoxemic group), and OSI (correlation coefficient -0.746, P value: 0.000 in hypoxemic group and correlation coefficient -0.629, P value: 0.000 in non-hypoxemic group) and has a positive correlation with P/F ratio (correlation coefficient 0.92, P value: 0.000 in hypoxemic group and correlation coefficient -0.67, P value: 0.000 in non-hypoxemic group). OI and OSI had a statistically significant correlation (correlation coefficient 0.955, P value: 0.000 in hypoxemic group and correlation coefficient 0.815, P value: 0.000 in non-hypoxemic group). on ROC analysis P/F ratio was the most accurate in predicting hypoxia followed by OI and OSI. with a cut-off value, of OI being 7.07, and that for OSI being 3.90, at an 80% sensitivity level to diagnose hypoxemia. CONCLUSION: OSI can serve as a dependable surrogate for OI, simplifying ARDS severity assessment. The P/F ratio is the most accurate predictor of hypoxia. Further research, especially in larger multicentre studies, is needed to validate these findings and explore the long-term clinical implications of using OSI for oxygenation monitoring in mechanically ventilated patients.

6.
Gastroenterol Hepatol (N Y) ; 20(2): 108-114, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38414912

ABSTRACT

Esophagogastric junction outflow obstruction (EGJOO) is a rapidly evolving diagnosis that can represent early or variant achalasia. Since the publication of the Chicago Classification version 4.0, the criteria for this diagnosis have been more stringent. Currently, the criteria include an elevated median integrated relaxation pressure (IRP) in both the supine and upright positions, elevated intrabolus pressure in at least 20% of supine swallows, dysphagia and/or chest pain, as well as an abnormal timed barium esophagram and/or impedance planimetry testing. Additionally, other secondary causes may result in an elevated IRP and must be excluded. The management of conclusive EGJOO is targeted therapy to the lower esophageal sphincter (LES), although treatment is not straightforward. Overall, adjuvant testing and data should be scrutinized for appropriateness of LES disruption. The spectrum of treatment options includes simple monitoring as well as more invasive therapies such as endoscopic dilation and myotomy. This article explores the newest criteria and management options for clinically relevant EGJOO.

7.
Surg Endosc ; 38(1): 291-299, 2024 01.
Article in English | MEDLINE | ID: mdl-37991572

ABSTRACT

BACKGROUND: Multiple factors contribute to symptom generation and treatment response in proton-pump inhibitor non-responders (PPI-NRs). We aimed to test whether PPI-NRs with normal acid exposure have a higher degree of esophageal hypersensitivity and hypervigilance and can be identified using functional lumen imaging probe (FLIP) topography at the time of endoscopy. METHODS: Data from PPI-NRs whom underwent endoscopy, FLIP and wireless 96-h pH-metry were retrospectively analyzed. Patients were grouped according to acid exposure time (AET) as (a) 0 days abnormal (AET > 6%), (b) 1-2 days abnormal, or (c) 3-4 days abnormal. The esophageal hypervigilance and anxiety scale (EHAS) score and other symptom scores were compared between groups. The discriminatory ability of the esophagogastric junction (EGJ) distensibility index (DI) and max EGJ diameter in identifying patients with 0 days abnormal AET was tested via receiver-operating-characteristic (ROC) curve analysis. RESULTS: EHAS score was 38.6 in the 0 days abnormal AET group, 30.4 in the 1-2 days abnormal AET group (p = 0.073 when compared to 0 days abnormal) and 28.2 in the 3-4 days abnormal AET group (p = 0.031 when compared to 0 days abnormal). Area-under-the-curve (AUC) for the DI in association with 0 days AET > 6% was 0.629. A DI of < 2.8 mm2/mmHg had a sensitivity of 83.3%, and negative predictive value of 88% in classifying patients with 0 days abnormal acid exposure (p = 0.004). CONCLUSIONS: FLIP complements prolonged wireless pH-metry in distinguishing the subset of PPI-NRs with completely normal acid exposure and a higher burden of esophageal hypervigilance. Proper identification of patients along the functional heartburn spectrum can improve overall surgical outcomes.


Subject(s)
Gastroesophageal Reflux , Humans , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/complications , Proton Pump Inhibitors/therapeutic use , Retrospective Studies , Esophageal pH Monitoring/methods
8.
Environ Res ; 241: 117726, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37984782

ABSTRACT

Land-terminating glaciers are retreating globally, resulting in the expansion of the ice-free glacier forelands (GFs). These GFs act as a natural laboratory to study microbial community succession, soil formation, and ecosystem development. Here, we have employed gene-centric and genome-resolved metagenomic approaches to disseminate microbial diversity, community structure, and their associated biogeochemical processes involved in the carbon, nitrogen, and sulfur cycling across three GF ecosystems. Here, we present a compendium of draft Metagenome Assembled Genomes (MAGs) belonging to bacterial (n = 899) and archaeal (n = 4) domains. These MAGs were reconstructed using a total of 27 shotgun metagenomic datasets obtained from three different GFs, including Midtre Lovénbreen glacier (Svalbard), Russell glacier (Greenland), and Storglaciaren (Sweden). The taxonomic classification revealed that 98% of MAGs remained unclassified at species levels, suggesting the presence of novel microbial lineages. The abundance of metabolic genes associated with carbon, nitrogen, and sulfur cycling pathways varied between and within the samples collected across the three GF ecosystems. Our findings indicate that MAGs from different GFs share close phylogenetic relationships but exhibit significant differences in abundance, distribution patterns, and metabolic functions. This compendium of novel MAGs, encompassing autotrophic, phototrophic, and chemolithoautotrophic microbial groups reconstructed from GF ecosystems, represents a valuable resource for further studies.


Subject(s)
Metagenome , Microbiota , Ice Cover/microbiology , Phylogeny , Microbiota/genetics , Carbon/metabolism , Sulfur , Nitrogen
9.
bioRxiv ; 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38076948

ABSTRACT

Diabetes is one of the most prevalent chronic diseases worldwide. Iron overload increases the incidence of diabetes and aggravates diabetic complications that cause mortality. Reciprocally, diabetes potentially promotes body iron loading, but the mechanism remains not well understood. In this study, we demonstrated systemic iron excess and the upregulation of iron exporter ferroportin (Fpn) in the enterocytes and macrophages of multiple diabetic mouse models. Increased Fpn expression and iron efflux was also seen in the enterocytes of type 2 diabetic human patients. We further showed that protein kinase C (PKC), which is activated in hyperglycemia, was responsible for the sustained membrane expression of Fpn in physiological and in diabetic settings. For the first time, we identified that PKCs were novel binding proteins and positive regulators of Fpn. Mechanistically, hyperactive PKC promoted exocytotic membrane insertion while inhibited the endocytic trafficking of Fpn in the resting state. PKC also protected Fpn from internalization and degradation by its ligand hepcidin dependent on decreased ubiquitination and increased phosphorylation of Fpn. Importantly, the loss-of-function and pharmacological inhibition of PKC alleviated systemic iron overload in diabetes and hemochromatosis. Our study thus highlights PKC as a novel target in the control of systemic iron homeostasis.

10.
World J Microbiol Biotechnol ; 40(1): 25, 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38057653

ABSTRACT

The thawing of snow and sea ice produces distinctive melt ponds on the surface of the Arctic sea ice, which covers a significant portion of the surface sea ice during summer. Melt-pond salinity impacts heat transfer to the ice below and the melting rate. It is widely known that melt ponds play a significant role in heat fluxes, ice-albedo feedback, and sea-ice energy balance. However, not much attention has been given to the fact that melt ponds also serve as a unique microbial ecosystem where microbial production begins as soon as they are formed. Here, we investigated the role of melt pond salinity in controlling the diversity and distribution of prokaryotic communities using culture-dependent and -independent approaches. The 16 S rRNA gene amplicon based next generation sequencing analysis retrieved a total of 14 bacterial phyla, consisting of 146 genera, in addition to two archaeal phyla. Further, the culture-dependent approaches of the study allowed for the isolation and identification of twenty-four bacterial genera in pure culture. Flavobacterium, Candidatus_Aquiluna, SAR11 clade, Polaribacter, Glaciecola, and Nonlabens were the dominant genera observed in the amplicon analysis. Whereas Actimicrobium, Rhodoglobus, Flavobacterium, and Pseudomonas were dominated in the culturable fraction. Our results also demonstrated that salinity, chlorophyll a, and dissolved organic carbon were the significant environmental variables controlling the prokaryotic community distribution in melt ponds. A significant community shift was observed in melt ponds when the salinity changed with the progression of melting and deepening of ponds. Different communities were found to be dominant in melt ponds with different salinity ranges. It was also observed that melt pond prokaryotic communities significantly differed from the surface ocean microbial community. Our observations suggest that complex prokaryotic communities develop in melt ponds immediately after its formation using dissolved organic carbon generated through primary production in the oligotrophic water.


Subject(s)
Flavobacteriaceae , Ponds , Ecosystem , Ice Cover/microbiology , Salinity , Chlorophyll A , Dissolved Organic Matter , Seawater/microbiology , Arctic Regions
11.
Extremophiles ; 27(3): 24, 2023 Sep 05.
Article in English | MEDLINE | ID: mdl-37668803

ABSTRACT

Archaea constitute a substantial fraction of marine microbial biomass and play critical roles in the biogeochemistry of oceans. However, studies on their distribution and ecology in the Arctic Ocean are relatively scarce. Here, we studied the distributions of archaea and archaeal ammonia monooxygenase (amoA) gene in the western Arctic Ocean, using the amplicon sequencing approach from the sea surface to deep waters up to 3040 m depth. A total of five archaeal phyla, Nitrososphaerota, "Euryarchaeota", "Halobacteriota," "Nanoarchaeota", and Candidatus Thermoplasmatota, were detected. We observed a clear, depth-dependent vertical segregation among archaeal communities. Ca. Thermoplasmatota (66.8%) was the most dominant phylum in the surface waters. At the same time, Nitrososphaerota (55.9%) was dominant in the deep waters. Most of the amoA gene OTUs (99%) belonged to the Nitrosopumilales and were further clustered into five subclades ("NP-Alpha", "NP-Delta", "NP-Epsilon", "NP-Gamma", and "NP-Theta"). "NP-Epsilon" was the most dominant clade throughout the water column and "NP_Alpha" showed higher abundance only in the deeper water. Salinity and inorganic nutrient concentrations were the major factors that determined the vertical segregation of archaea. We anticipate that the observed differences in the vertical distribution of archaea might contribute to the compartmentalization of dark carbon fixation and nitrification in deeper water and organic matter degradation in surface waters of the Arctic Ocean.


Subject(s)
Archaea , Euryarchaeota , Archaea/genetics , Phylogeny , Water
12.
Microb Ecol ; 86(4): 2733-2746, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37532947

ABSTRACT

Nitrogen-fixing or diazotrophic microbes fix atmospheric nitrogen (N2) to ammonia (NH3+) using nitrogenase enzyme and play a crucial role in regulating marine primary productivity and carbon dioxide sequestration. However, there is a lack of information about the diversity, structure, and environmental regulations of the diazotrophic communities in the high Arctic fjords, such as Kongsfjorden. Here, we employed nifH gene sequencing to clarify variations in composition, community structure, and assembly mechanism among the diazotrophs of the salinity-driven stratified waters of Kongsfjorden. The principal environmental and ecological drivers of the observed variations were identified. The majority of the nifH gene sequences obtained in the present study belonged to cluster I and cluster III nifH phylotypes, accounting for 65% and 25% of the total nifH gene sequences. The nifH gene diversity and composition, irrespective of the size fractions (free-living and particle attached), showed a clear separation among water mass types, i.e., Atlantic-influenced versus glacier-influenced water mass. Higher nifH gene diversity and relative abundances of non-cyanobacterial nifH OTUs, affiliated with uncultured Rhizobiales, Burkholderiales, Alteromonadaceae, Gallionellaceae (cluster I) and uncultured Deltaproteobacteria including Desulfuromonadaceae (cluster III), were prevalent in GIW while uncultured Gammaproteobacteria and Desulfobulbaceae were abundant in AIW. The diazotrophic community assembly was dominated by stochastic processes, principally ecological drift, and to lesser degrees dispersal limitation and homogeneous dispersal. Differences in the salinity and dissolved oxygen content lead to the vertical segregation of diazotrophs among water mass types. These findings suggest that water column stratification affects the composition and assembly mechanism of diazotrophic communities and thus could affect nitrogen fixation in the Arctic fjord.


Subject(s)
Estuaries , Water , Svalbard , Nitrogen Fixation/genetics , Nitrogen , Stochastic Processes
13.
ACG Case Rep J ; 10(4): e01022, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37057194
14.
Am J Gastroenterol ; 118(8): 1334-1343, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37042784

ABSTRACT

INTRODUCTION: High-resolution manometry (HRM) and functional lumen imaging probe (FLIP) are primary and/or complementary diagnostic tools for the evaluation of esophageal motility. We aimed to assess the interrater agreement and accuracy of HRM and FLIP interpretations. METHODS: Esophageal motility specialists from multiple institutions completed the interpretation of 40 consecutive HRM and 40 FLIP studies. Interrater agreement was assessed using intraclass correlation coefficient (ICC) for continuous variables and Fleiss' κ statistics for nominal variables. Accuracies of rater interpretation were assessed using the consensus of 3 experienced raters as the reference standard. RESULTS: Fifteen raters completed the HRM and FLIP studies. An excellent interrater agreement was seen in supine median integral relaxation pressure (ICC 0.96, 95% confidence interval 0.95-0.98), and a good agreement was seen with the assessment of esophagogastric junction (EGJ) outflow, peristalsis, and assignment of a Chicago Classification version 4.0 diagnosis using HRM (κ = 0.71, 0.75, and 0.70, respectively). An excellent interrater agreement for EGJ distensibility index and maximum diameter (0.91 [0.90-0.94], 0.92 [0.89-0.95]) was seen, and a moderate-to-good agreement was seen in the assignment of EGJ opening classification, contractile response pattern, and motility classification (κ = 0.68, 0.56, and 0.59, respectively) on FLIP. Rater accuracy for Chicago Classification version 4.0 diagnosis on HRM was 82% (95% confidence interval 78%-84%) and for motility diagnosis on FLIP Panometry was 78% (95% confidence interval 72%-81%). DISCUSSION: Our study demonstrates high levels of interrater agreement and accuracy in the interpretation of HRM and FLIP metrics and moderate-to-high levels for motility classification in FLIP, supporting the use of these approaches for primary or complementary evaluation of esophageal motility disorders.


Subject(s)
Esophageal Achalasia , Esophageal Motility Disorders , Humans , Reproducibility of Results , Esophageal Motility Disorders/diagnosis , Esophagogastric Junction/diagnostic imaging , Manometry/methods , Peristalsis , Esophageal Achalasia/diagnosis
15.
J Anim Breed Genet ; 140(4): 400-412, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36883272

ABSTRACT

In the present study, random regression models (RRM) were used to estimate genetic parameters for test-day milk yield in Murrah buffaloes using Legendre polynomial function (LP), with the objective to find the best combination of "minimum test-day model," which would be essential and sufficient to evaluate the trait successfully. Data included for analysis were 10,615 first lactation monthly test-day milk yield records (5th, 35th, 65th, …, 305th) from 965 Murrah buffaloes for the period 1975-2018. Cubic to octic-order orthogonal polynomials with homogeneous residual variances were used for the estimation of genetic parameters. Random regression models with sixth-order were selected based on goodness of fit criteria like lower AIC, BIC and residual variance. Heritability estimates ranged from 0.079 (TD6) to 0.21(TD10). For both ends of lactation, the additive genetic and environmental variances were higher and ranged from 0.21 ± 0.12 (TD6) to 0.85 ± 0.35 kg2 (TD1) and 3.74 ± 0.36 (TD11) to 1.36 ± 0.14 kg2 (TD9), respectively. Between adjacent test-day records, genetic correlation estimates ranged from 0.09 ± 0.31 (TD1 and TD2) to 0.97 ± 0.03 (TD3 and TD4; TD4 and TD5), but values gradually declined as the distance between test days increased. Negative genetic correlations were also obtained between TD1 with TD3 to TD9, TD2 with TD9 and TD10, and TD3 with TD10. On the basis of genetic correlations, models with 5 and/or 6 test-days combination were able to account for 86.1%-98.7% of variation along the lactation. Models with fourth and fifth-order LP functions were considered to account for variance with combinations of 5 and/or 6 test-day milk yields. The model with 6 test-day combinations had a higher rank correlation (0.93) with model using 11 monthly test-day milk yield records. On the basis of relative efficiency, the model with 6 monthly test day combinations with fifth-order was more efficient (maximum 99%) than the model using 11 monthly test-day milk yield records. Looking into the similar accuracy with the 11TD model, and the low resources requirement, we recommend the use of the "6 test-day combination model" for sire evaluation. These models may help in reducing the cost and time for data recording of milk yield.


Subject(s)
Buffaloes , Milk , Female , Animals , Buffaloes/genetics , Quantitative Trait, Heritable , Lactation/genetics , Phenotype
16.
Anim Biotechnol ; 34(8): 3545-3554, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36794377

ABSTRACT

India has a centuries-old tradition of sheep production and breeding that accomplish economic, agricultural, and religious roles. In addition to the 44 registered sheep breeds, there is a fat-tailed sheep population referred to as Dumba. This study evaluated genetic variation in Dumba sheep and its differentiation from other Indian sheep breeds using mitochondrial DNA and genomic microsatellite loci. Haplotype and nucleotide diversity based on mitochondrial DNA analysis revealed substantially high maternal genetic diversity in Dumba sheep. Major ovine haplogroups A and B observed in sheep populations across the globe registered their presence in the Dumba sheep. The molecular genetic analysis using microsatellite markers also showed high measures of allele (10.125 ± 0.762) and gene diversity (0.749 ± 0.029). Results correspond to the non-bottleneck population that is near mutation-drift equilibrium despite some deficiency in the number of heterozygotes (FIS = 0.043 ± 0.059). Phylogenetic clustering confirmed Dumba to be a distinct population. Results of this study endow authorities with critical information imperative for sustainable utilization and conservation of Indian fat-tailed sheep, which is considered to be an untapped genetic resource contributing to the food security, livelihood, and economic sustainability of rural households in marginal areas of the country.


Subject(s)
DNA, Mitochondrial , Genetic Variation , Sheep/genetics , Animals , Genetic Variation/genetics , Phylogeny , DNA, Mitochondrial/genetics , Microsatellite Repeats/genetics , India
17.
Gastrointest Endosc ; 97(2): 251-259, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36228696

ABSTRACT

BACKGROUND AND AIMS: Treatment options for nonachalasia obstructive disorders of the esophagogastric junction (EGJ) are limited. The aim of this study was to assess the treatment efficacy of pneumatic dilation (PD) for the disorders of EGJ outflow obstruction (EGJOO) and postfundoplication EGJ obstruction (PF-EGJO) and to assess attitudes regarding training in PD. METHODS: This was a 2-part study. The main study was a prospective, single-center study comparing treatment outcomes after PD in patients with EGJOO and PF-EGJO, defined using manometry criteria, versus achalasia. Treatment success was defined as a post-PD Eckardt score (ES) of ≤2 at the longest duration of follow-up available. In a substudy, a 2-question survey was sent to 78 advanced endoscopy fellowship sites in the United States regarding training in PD. RESULTS: Of the 58% of respondents to the advanced endoscopy program director survey, two-thirds reported no training in PD at their program. The primary rationale cited was lack of a clinical need for PD. Sixty-one patients (15 achalasia, 32 EGJOO, and 14 PF-EGJO) were included in the main study with outcomes available at a mean follow-up of 8.8 months. Overall, mean ES decreased from 6.30 to 2.89 (P < .0001), and a mean percentage of improvement in symptoms reported by patients was 55.3%. ES ≤2 was achieved by 33 of 61 patients (54.1%). CONCLUSIONS: PD is an effective treatment for the nonachalasia obstructive disorders of the EGJ. There may be a current gap in training and technical expertise in PD.


Subject(s)
Esophageal Achalasia , Esophageal Motility Disorders , Humans , Prospective Studies , Dilatation , Esophagogastric Junction , Manometry
18.
Am J Gastroenterol ; 117(10): 1573-1582, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35973148

ABSTRACT

INTRODUCTION: Ambulatory reflux monitoring performed off proton pump inhibitor (PPI) is the gold standard diagnostic test for nonerosive gastroesophageal reflux disease (GERD). However, the diagnostic metrics and optimal duration of monitoring are not well defined. This study evaluated the performance of multiple metrics across distinct durations of wireless reflux monitoring off PPI against the ability to discontinue PPI therapy in patients with suboptimal PPI response. METHODS: This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to > 8 weeks of PPI. Participants underwent 96-hour wireless pH monitoring off PPI. Primary outcome was whether the subject successfully discontinued PPI or resumed PPI within 3 weeks. RESULTS: Of 132 participants, 30% discontinued PPI. Among multiple metrics assessed, total acid exposure time (AET) of 4.0% performed best in predicting PPI discontinuation (odds ratio 2.9 [95% confidence interval 1.4, 6.4]; P = 0.006), with other thresholds of AET and DeMeester score performing comparably. AET was significantly higher on day 1 of monitoring compared with other days, and prognostic performance significantly declined when only assessing the first 48 hours of monitoring (area under the curve for 96 hours 0.63 vs area under the curve for 48 hours 0.57; P = 0.01). DISCUSSION: This clinical trial highlights the AET threshold of 4.0% as a high-performing prognostic marker of PPI discontinuation. 96 hours of monitoring performed better than 48 hours, in predicting ability to discontinue PPI. These data can inform current diagnostic approaches for patients with GERD symptoms who are unresponsive to PPI therapy.


Subject(s)
Esophageal pH Monitoring , Gastroesophageal Reflux , Adult , Humans , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/drug therapy , Prognosis , Proton Pump Inhibitors/therapeutic use
19.
Aliment Pharmacol Ther ; 56(8): 1274-1283, 2022 10.
Article in English | MEDLINE | ID: mdl-35971888

ABSTRACT

BACKGROUND: Optimal ambulatory reflux monitoring methodology in symptomatic reflux patients continues to be debated. AIMS: To utilise published literature and expert opinion to develop recommendation statements addressing use of ambulatory reflux monitoring in clinical practice METHODS: The RAND Appropriateness Method (RAM) was utilised among 17 experts with discussion, revision and two rounds of ranking of recommendation statements. Ambulatory reflux monitoring protocol, methodology and thresholds ranked as appropriate by ≥80% of panellists met the criteria for appropriateness. RESULTS: Prolonged (96-h recommended) wireless pH monitoring off proton pump inhibitor (PPI) was identified as the appropriate diagnostic tool to assess the need for acid suppression in patients with unproven gastro-oesophageal reflux disease (GERD) and persisting typical reflux symptoms despite once-daily PPI. Acid exposure time (AET) <4.0% on all days of monitoring with negative reflux-symptom association excludes GERD and does not support ongoing PPI treatment. Conversely, AET >6.0% across ≥2 days is conclusive evidence for GERD and supports treatment for GERD, while AET >10% across ≥2 days identifies severe acid burden that supports escalation of anti-reflux treatment. In previously proven GERD, impedance-pH monitoring on PPI is helpful in defining refractory GERD and mechanisms of continued symptoms; the presence of <40 reflux events, AET <2.0% and a negative reflux-symptom association does not support escalation of anti-reflux treatment. In contrast, AET > 4.0% and positive reflux-symptom association support escalation of anti-reflux treatment, including use of invasive therapeutics. CONCLUSIONS: Statements meeting appropriateness for average clinical care have been identified when utilising reflux monitoring in patients with typical reflux symptoms and PPI non-response.


Subject(s)
Esophagitis, Peptic , Gastroesophageal Reflux , Humans , Esophageal pH Monitoring , Esophagitis, Peptic/drug therapy , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/drug therapy , Proton Pump Inhibitors/therapeutic use
20.
Indian J Crit Care Med ; 26(6): 696-703, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35836625

ABSTRACT

Purpose: End-organ damage in coronavirus disease-2019 (COVID-19) is linked to "cytokine storm" and excessive release of inflammatory mediators. Various novel therapies have been used in COVID-19 including urinary trypsin inhibitor therapy. This study explores the efficacy of ulinastatin in COVID-19. Materials and methods: We retrieved the medical records of patients admitted during one month and did a propensity score analysis to create matched treatment and control groups. We analyzed these groups and the outcomes were presented with appropriate statistics. Survival curve was prepared to compare the survival effect of ulinastatin therapy at the end of hospitalization, among both the groups. Results: A total of 736 patients were admitted, and after adjusting the data with propensity score matching, 55 cases were selected by the system. On the final outcome analysis, we found that intensive care unit (ICU) length of stay [median (interquartile range) days 3 (3.5-7.8) vs 2 (0-4); p-value 0.28] in control vs intervention groups, and in hospital mortality (odds ratio: 0.491, CI 95%: 0.099-2.44, p-value 0.435) were not statistically different among the groups. In survival plot analysis also, there was no statistical difference (p-value 0.414) among both the groups.Conclusion: In this retrospective study, we conclude that the final outcome of the ICU length of stay, and overall, in hospital mortality were not different among both the groups. Hence, adequately powered randomized control trials are urgently required to confirm any benefit of ulinastatin therapy in COVID-19 treatment. How to cite this article: Jain A, Kasliwal R, Jain SS, Jain R, Gupta D, Gupta P, et al. Effect of Urinary Trypsin Inhibitor (Ulinastatin) Therapy in COVID-19. Indian J Crit Care Med 2022;26(6):696-703.

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