Survival bias may explain the appearance of the obesity paradox in hip fracture patients.

Patients with low-energy hip fractures do not follow the obesity paradox as previously reported. In datasets where injury mechanism is not available, the use of age >50 years (as opposed to commonly used >65 years) as a surrogate for a low-energy hip fracture patients may be a more robust inclusion criterion. PURPOSE: In elderly patients with a hip fracture, limited data suggests that obese patients counterintuitively have improved survival compared to normal-weight patients. This "obesity paradox" may be the byproduct of selection bias. We hypothesized that the obesity paradox would not apply to elderly hip fracture patients. METHODS: The National Surgical Quality Improvement Project dataset identified 71,685 hip fracture patients ≥50 years-of-age with complete body mass index (BMI) data that underwent surgery. Patients were stratified into under and over 75-year-old cohorts (n=18,956 and 52,729, respectively). Within each age group, patients were stratified by BMI class and compared with respect to preoperative characteristics and 30-day mortality. Significant univariate characteristics (p<0.1) were included in multivariate analysis to determine the independent effect of obesity class on 30-day mortality (p<0.05). RESULTS: Multivariate analysis of <75-year-old patients with class-III obesity were more likely to die within 30-days than similarly aged normal-weight patients (OR 1.91, CI 1.06-3.42, p=0.030). Multivariate analysis of ≥75-year-old overweight (OR 0.69, CI 0.62-0.77, p<0.001), class-I obese (OR 0.62, CI 0.51-0.74, p<0.001), or class-II obese (OR=0.69, CI 0.50-0.95, p=0.022) patients were less likely to die within 30-days when compared to similarly aged normal-weight patients. CONCLUSIONS: Our data suggest that obesity is a risk factor for mortality in low-energy hip fracture patients, but the appearance of the "obesity paradox" in elderly hip fracture patients results from statistical bias that is only evident upon subgroup analysis.

Indian Resuscitation Council (IRC) suggested guidelines for Comprehensive Cardiopulmonary Life Support (CCLS) for suspected or confirmed coronavirus disease (COVID-19) patient.

Management of the recent outbreak of the novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) remains challenging. The challenges are not only limited to its preventive strategies, but also extend to curative treatment, and are amplified during the management of critically ill patients with COVID-19. Older persons with comorbidities like diabetes mellitus, cardiac diseases, hepatic impairment, renal disorders and respiratory pathologies or immune impairing conditions are more vulnerable and have a higher mortality from COVID-19. Earlier, the Indian Resuscitation Council (IRC) had proposed the Comprehensive Cardiopulmonary Life Support (CCLS) for management of cardiac arrest victims in the hospital setting. However, in patients with COVID-19, the guidelines need to be modified,due to various concerns like differing etiology of cardiac arrest, virulence of the virus, risk of its transmission to rescuers, and the need to avoid or minimize aerosolization from the patient due to various interventions. There is limited evidence in these patients, as the SARS-CoV-2 is a novel infection and not much literature is available with high-level evidence related to CPR in patients of COVID-19. These suggested guidelines are a continuum of CCLS guidelines by IRC with an emphasis on the various challenges and concerns being faced during the resuscitative management of COVID-19 patients with cardiopulmonary arrest.

Cross-country transport and isolation and identification of Streptococcus pneumoniae by use of alternate sources of blood supplemented media among laboratories in India.

Background: The isolation of S. pneumoniae (Sp) depends on specimen integrity / transport, media and expertise. The non-availability of sheep blood agar poses a challenge in identification of colonial morphology and identification in India. Methods: Laboratories processed swabs containing either pure Sp or Sp in mixed cultures with a second (confounding) bacterium shipped across the country in cold conditions. Duplicate set of swabs was shipped back to the central laboratory to assess the impact of shipping on culture viability. The identical swab was cultured on sheep, human blood and one additional agar plate used in the laboratory. Results: 46/60(77%) of cultures containing only Sp were correctly identified. In specimens where Sp was present in mixed culture, the proportion of isolates in which Sp was correctly identified varied, with most variability attributed to the particular confounding organism rather than the media. There was no discernible impact of temperature-controlled (4-6°C) transport on the isolation of Sp from culture swabs. Conclusions: The study clearly elucidates the ability of laboratories for isolation of S. pneumoniae on human blood agar in resource limited settings. The results highlight the difficulties inherent in correctly identifying pathogens in mixed cultures in needs improvement using standardized tests across the study centers. The study also reaffirms the ability to transport biological specimens over long geographical distances without loss.

A high-resolution anorectal manometry parameter based on integrated pressurized volume: A study based on 204 male patients with constipation and 26 controls.

BACKGROUND: Conventional anorectal manometric parameters based on linear waves cannot properly predict balloon expulsion (BE) time. We aimed to determine the correlation between integrated pressurized volume (IPV) parameters during simulated evacuation (SE) and BE time in healthy individuals and constipated patients and to assess the correlation between each parameter and symptoms. METHODS: A total of 230 male participants (including 26 healthy volunteers and 204 chronically constipated patients) underwent high-resolution anorectal manometry (HRAM) and BE tests. The IPV was calculated by multiplying the amplitude, distance, and time from the HRAM profile. Receiver operating characteristic curve (ROC) analysis and partial least square regression (PLSR) were performed. KEY RESULTS: ROC analysis indicated that the IPV ratio between the upper 1 cm and lower 4 cm of the anal canal was more effective for predicting BE time (area under the curve [AUC]: 0.74, 95% confidence interval [CI]: 0.67-0.80, P < .01) than the conventional anorectal parameters, including defecation index and rectoanal gradient (AUC: 0.60, 95% CI: 0.52-0.67, P = .01). PLSR analysis of a linear combination of IPV parameters yielded an AUC of 0.79. Moreover, the IPV ratio showed a greater clinical correlation with patient symptoms than conventional parameters. CONCLUSIONS AND INFERENCES: The IPV parameters and the combination of IPV parameters via PLSR were more significantly correlated with BE time than the conventional parameters. Thus, this study presents a useful diagnostic tool for the evaluation of pathophysiologic abnormalities in dyssynergic defecation using IPV and BE time.

Development, content validity, and cross-cultural adaptation of a patient-reported outcome measure for real-time symptom assessment in irritable bowel syndrome.

BACKGROUND: End-of-day questionnaires, which are considered the gold standard for assessing abdominal pain and other gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS), are influenced by recall and ecological bias. The experience sampling method (ESM) is characterized by random and repeated assessments in the natural state and environment of a subject, and herewith overcomes these limitations. This report describes the development of a patient-reported outcome measure (PROM) based on the ESM principle, taking into account content validity and cross-cultural adaptation. METHODS: Focus group interviews with IBS patients and expert meetings with international experts in the fields of neurogastroenterology & motility and pain were performed in order to select the items for the PROM. Forward-and-back translation and cognitive interviews were performed to adapt the instrument for the use in different countries and to assure on patients' understanding with the final items. KEY RESULTS: Focus group interviews revealed 42 items, categorized into five domains: physical status, defecation, mood and psychological factors, context and environment, and nutrition and drug use. Experts reduced the number of items to 32 and cognitive interviewing after translation resulted in a few slight adjustments regarding linguistic issues, but not regarding content of the items. CONCLUSIONS AND INFERENCES: An ESM-based PROM, suitable for momentary assessment of IBS symptom patterns was developed, taking into account content validity and cross-cultural adaptation. This PROM will be implemented in a specifically designed smartphone application and further validation in a multicenter setting will follow.

Cellulase production through solid-state tray fermentation, and its use for bioethanol from sorghum stover.

The production of cellulase by Trichoderma reesei RUT C-30 under solid-state fermentation (SSF) on wheat bran and cellulose was optimized employing a two stage statistical design of experiments. Optimization of process parameters resulted in a 3.2-fold increase in CMCase production to 959.53IU/gDS. The process was evaluated at pilot scale in tray fermenters and yielded 457IU/gDS using the lab conditions and indicating possibility for further improvement. The cellulase could effectively hydrolyze alkali pretreated sorghum stover and addition of Aspergillus niger ß-glucosidase improved the hydrolytic efficiency 174%, indicating the potential to use this blend for effective saccharification of sorghum stover biomass. The enzymatic hydrolysate of sorghum stover was fermented to ethanol with ∼80% efficiency.

Methods of anorectal manometry vary widely in clinical practice: Results from an international survey.

BACKGROUND: Ano-rectal manometry (ARM) is the most commonly performed investigation for assessment of anorectal dysfunction. Its use is supported by expert consensus documents and international guidelines. Variation in technology, data acquisition, and analysis affect results and clinical interpretation. This study examined variation in ARM between institutions to establish the status of current practice. METHODS: A 50-item web-based questionnaire assessing analysis and interpretation of ARM was distributed by the International Anorectal Physiology Working Group via societies representing practitioners that perform ARM. Study methodology and performance characteristics between institutions were compared. KEY RESULTS: One hundred and seven complete responses were included from 30 countries. Seventy-nine (74%) institutions performed at least two studies per week. Forty-nine centers (47%) applied conventional ARM (≤8 pressure sensors) and 57 (53%) high-resolution ARM (HR-ARM). Specialist centers were most likely to use HR-ARM compared to regional hospitals and office-based practice (63% vs 37%). Most conventional ARM systems used water-perfused technology (34/49); solid-state hardware was more frequently used in centers performing HR-ARM (44/57). All centers evaluated rest and squeeze. There was marked variation in the methods used to report results of maneuvers. No two centers had identical protocols for patient preparation, setup, study, and data interpretation, and no center fully complied with published guidelines. CONCLUSIONS & INFERENCES: There is significant discrepancy in methods for data acquisition, analysis, and interpretation of ARM. This is likely to impact clinical interpretation, transfer of data between institutions, and research collaboration. There is a need for expert international co-operation to standardize ARM.

Calpain-activated mTORC2/Akt pathway mediates airway smooth muscle remodelling in asthma.

BACKGROUND: Allergic asthma is characterized by inflammation and airway remodelling. Airway remodelling with excessive deposition of extracellular matrix (ECM) and larger smooth muscle mass are correlated with increased airway responsiveness and asthma severity. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodelling. However, the role of calpain in airway smooth muscle remodelling remains unknown. OBJECTIVE: To investigate the role of calpain in asthmatic airway remodelling as well as the underlying mechanism. METHODS: The mouse asthma model was made by ovalbumin sensitization and challenge. Calpain conditional knockout mice were studied in the model. Airway smooth muscle cells (ASMCs) were isolated from smooth muscle bundles in airway of rats. Cytokines IL-4, IL-5, TNF-α, and TGF-ß1, and serum from patients with asthma were selected to treated ASMCs. Collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs were analysed. RESULTS: Inhibition of calpain using calpain knockout mice attenuated airway smooth muscle remodelling in mouse asthma models. Cytokines IL-4, IL-5, TNF-α, and TGF-ß1, and serum from patients with asthma increased collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs, which were blocked by the calpain inhibitor MDL28170. Moreover, MDL28170 reduced cytokine-induced increases in Rictor protein, which is the most important component of mammalian target of rapamycin complex 2 (mTORC2). Blockage of the mTORC2 signal pathway prevented cytokine-induced phosphorylation of Akt, collagen-I synthesis, and cell proliferation of ASMCs and attenuated airway smooth muscle remodelling in mouse asthma models. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate that calpain mediates cytokine-induced collagen-I synthesis and proliferation of ASMCs via the mTORC2/Akt signalling pathway, thereby regulating airway smooth muscle remodelling in asthma.

Molecular analysis of Rv0679c and Rv0180c genes of Mycobacterium tuberculosis from clinical isolates of pulmonary tuberculosis.

CONTEXT: Two novel proteins/genes Rv0679c and Rv0180c of Mycobacterium tuberculosis (MTB) H37Rv were classified as a hypothetical membrane and transmembrane proteins which might have a role in the invasion. Molecular analysis of these genes in human clinical isolates of pulmonary tuberculosis (PTB) patients was not well characterised. AIMS: To assess the molecular diversity of Rv0679c and Rv0180c genes of MTB from clinical isolates of PTB patients. SETTINGS AND DESIGN: DNA from 97 clinical isolates was extracted and subjected to amplification using selective primers by polymerase chain reaction (PCR). The PCR product obtained was sequenced commercially. PATIENTS AND METHODS: Clinical isolates obtained from tuberculosis patients were investigated for polymorphisms in the Rv0679c and Rv0180c genes by PCR and DNA sequencing. Genomic DNA isolated by cetyltrimethylammonium bromide method was used for amplification of genes. RESULTS: Rv0679c gene was highly conserved in 61 out of 65 clinical isolates assessed for sequence homology with wild-type H37Rv gene and was identical using ClustalW. Fifty-five out of 78 (70.5%) clinical isolates assessed for Rv0180c were positive for single nucleotide polymorphism (SNP) at 258th position where the nucleotide G was replaced with T (G to T). In clinical isolates of untreated cases, the frequency was 54.5% for SNP at 258th position which is low compared to cases undergoing treatment where the frequency was 73.1%. CONCLUSIONS: Molecular analysis of Rv0180c in clinical isolates of PTB assessed in this study was the first report, where an SNP at 258th position G to T was identified within the gene. Rv0679c gene was highly conserved (94%), within Indian clinical isolates as compared to reports from other nations.

Endpoints for therapeutic interventions in faecal incontinence: small step or game changer.

Faecal incontinence (FI) is common and its pathophysiology and treatments continue to evolve. However, a standard measure(s) for assessing its clinical outcome has been elusive. Consequently, over 100 measures and scoring systems, each with intrinsic biases have been reported. These include adequate relief or global satisfaction, ≥50% reduction in episodes or days without FI, quality of life (QOL), FI severity scales and composite indices. Earlier scales relied on the frequency and type of solid, liquid or flatus incontinence and effects on life style whereas newer scales have incorporated urgency, use of pads, antidiarrhoeals and amount of leakage, using prospective daily stool diaries or retrospective weekly or single point assessments. Such a plethora of measures have negatively impacted the assessment and outcome of clinical trials, and have made comparisons difficult. So, how does one sort out the grain from the chaff? In a provocative, post-hoc analysis published in this issue, the minimal clinically important difference, i.e. the smallest change detected by an instrument that is associated with a clinically meaningful change was used to assess FI endpoint. Based on this a ≥50% reduction in FI episodes is recommended as a clinically meaningful outcome measure when assessed by prospective stool diary, and it correlates with symptoms and severity. However, this requires further validation in multi-centre, longer duration and therapeutically effective clinical trial(s). Simultaneous assessment of coping strategies, QOL and psychosocial domains can provide further insights regarding the overall impact of treatments. This mini-review discusses the advances and controversies in defining meaningful FI endpoints.

Randomised clinical trial: mixed soluble/insoluble fibre vs. psyllium for chronic constipation.

BACKGROUND: Fibre supplements are useful, but whether a plum-derived mixed fibre that contains both soluble and insoluble fibre improves constipation is unknown. AIM: To investigate the efficacy and tolerability of mixed soluble/insoluble fibre vs. psyllium in a randomized double-blind controlled trial. METHODS: Constipated patients (Rome III) received mixed fibre or psyllium, 5 g b.d., for 4 weeks. Daily symptoms and stool habit were assessed using stool diary. Subjects with ≥1 complete spontaneous bowel movement/week above baseline for ≥2/4 weeks were considered responders. Secondary outcome measures included stool consistency, bowel satisfaction, straining, gas, bloating, taste, dissolvability and quality of life (QoL). RESULTS: Seventy-two subjects (mixed fibre = 40; psyllium = 32) were enrolled and two from psyllium group withdrew. The mean complete spontaneous bowel movement/week increased with both mixed fibre (P < 0.0001) and psyllium (P = 0.0002) without group difference. There were 30 (75%) responders with mixed fibre and 24 (75%) with psyllium (P = 0.9). Stool consistency increased (P = 0.04), straining (P = 0.006) and bloating scores decreased (P = 0.02) without group differences. Significantly more patients reported improvement in flatulence (53% vs. 25%, P = 0.01) and felt that mixed fibre dissolved better (P = 0.02) compared to psyllium. QoL improved (P = 0.0125) with both treatments without group differences. CONCLUSIONS: Mixed fibre and psyllium were equally efficacious in improving constipation and QoL. Mixed fibre was more effective in relieving flatulence, bloating and dissolved better. Mixed fibre is effective and well tolerated.

Regional gastrointestinal transit and pH studied in 215 healthy volunteers using the wireless motility capsule: influence of age, gender, study country and testing protocol.

BACKGROUND: The wireless motility capsule (WMC) offers the ability to investigate luminal gastrointestinal (GI) physiology in a minimally invasive manner. AIM: To investigate the effect of testing protocol, gender, age and study country on regional GI transit times and associated pH values using the WMC. METHODS: Regional GI transit times and pH values were determined in 215 healthy volunteers from USA and Sweden studied using the WMC over a 6.5-year period. The effects of test protocol, gender, age and study country were examined. RESULTS: For GI transit times, testing protocol was associated with differences in gastric emptying time (GET; shorter with protocol 2 (motility capsule ingested immediately after meal) vs. protocol 1 (motility capsule immediately before): median difference: 52 min, P = 0.0063) and colonic transit time (CTT; longer with protocol 2: median 140 min, P = 0.0189), but had no overall effect on whole gut transit time. Females had longer GET (by median 17 min, P = 0.0307), and also longer CTT by (104 min, P = 0.0285) and whole gut transit time by (263 min, P = 0.0077). Increasing age was associated with shorter small bowel transit time (P = 0.002), and study country also influenced small bowel and CTTs. Whole gut and CTTs showed clustering of data at values separated by 24 h, suggesting that describing these measures as continuous variables is invalid. Testing protocol, gender and study country also significantly influenced pH values. CONCLUSIONS: Regional GI transit times and pH values, delineated using the wireless motility capsule (WMC), vary based on testing protocol, gender, age and country. Standardisation of testing is crucial for cross-referencing in clinical practice and future research.

Systematic review: dietary fibre and FODMAP-restricted diet in the management of constipation and irritable bowel syndrome.

BACKGROUND: Dietary fibre supplements have been advocated for the management of chronic constipation (CC) and irritable bowel syndrome (IBS). Recently, a fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) restricted diet has been recommended for IBS. AIM: To systematically examine recent evidence for dietary interventions with fibre in CC and IBS and FODMAP-restricted diet in IBS, and provide recommendations. METHODS: We searched PUBMED, MEDLINE, OVID and COCHRANE databases from 2004 to 2014. Published studies in adults with CC and IBS and constipation-predominant IBS (IBS-C) that compared fibre with placebo/alternative and FODMAP-restricted diet with alternative were included. RESULTS: Of 550 potentially eligible clinical trials on fibre, 11 studies were found and of 23 potentially eligible studies on FODMAPs, six were found. A meta-analysis was not performed due to heterogeneity and methodological quality. Fibre was beneficial in 5/7 studies in CC and 3/3 studies in IBS-C. FODMAP-restricted diet improved overall IBS symptoms in 4/4 and IBS-C symptoms in 1/3 studies and three studies did not meet inclusion criteria. There were significant disparities in subject selection, interventions and outcome assessments in both fibre and FODMAPs studies. CONCLUSIONS: Fibre supplementation is beneficial in mild to moderate CC and IBS-C, although larger, more rigorous and long-term RCTs are needed (Fair evidence-Level II, Grade B). Although the FODMAP-restricted diet may be effective in short-term management of selected patients with IBS (Fair evidence-Level II, Grade C) and IBS-C (Poor evidence-Level III, Grade C), more rigorous trials are needed to establish long-term efficacy and safety, particularly on colonic health and microbiome.

ANMS-ESNM position paper and consensus guidelines on biofeedback therapy for anorectal disorders.

BACKGROUND: Anorectal disorders such as dyssynergic defecation, fecal incontinence, levator ani syndrome, and solitary rectal ulcer syndrome are common, and affect both the adult and pediatric populations. Although they are treated with several treatment approaches, over the last two decades, biofeedback therapy using visual and verbal feedback techniques has emerged as an useful option. Because it is safe, it is commonly recommended. However, the clinical efficacy of biofeedback therapy in adults and children is not clearly known, and there is a lack of critical appraisal of the techniques used and the outcomes of biofeedback therapy for these disorders. PURPOSE: The American Neurogastroenterology and Motility Society and the European Society of Neurogastroenterology and Motility convened a task force to examine the indications, study performance characteristics, methodologies used, and the efficacy of biofeedback therapy, and to provide evidence-based recommendations. Based on the strength of evidence, biofeedback therapy is recommended for the short-term and long-term treatment of constipation with dyssynergic defecation (Level I, Grade A), and for the treatment of fecal incontinence (Level II, Grade B). Biofeedback therapy may be useful in the short-term treatment of Levator Ani Syndrome with dyssynergic defecation (Level II, Grade B), and solitary rectal ulcer syndrome with dyssynergic defecation (Level III, Grade C), but the evidence is fair. Evidence does not support the use of biofeedback for the treatment of childhood constipation (Level 1, Grade D).

Small intestinal bacterial overgrowth: duodenal aspiration vs glucose breath test.

BACKGROUND: The diagnosis of small intestinal bacterial overgrowth (SIBO) remains challenging. Our aim was to examine the diagnostic yield of duodenal aspiration/culture and glucose breath test (GBT), and effects of gender, race and demographics on prevalence of SIBO. METHODS: Patients with unexplained gas, bloating and diarrhea and negative endoscopy, imaging and blood tests were prospectively enrolled in two centers in USA. Randomly, within 1 week each patient underwent both duodenal aspiration/culture and GBT. The diagnostic yield of each test and relationship of symptoms, and effects of ethnicity, age, and gender on prevalence of SIBO were assessed and compared. KEY RESULTS: Duodenal culture was positive in 62/139 (44.6%) subjects and GBT was positive in 38/139 (27.3%) subjects with an overall diagnostic agreement of 65.5%. The sensitivity, specificity, positive and negative predictive value of GBT was 42%, 84%, 68%, and 64%, respectively. Ethnicity or gender did not influence SIBO, but SIBO positive patients were older (p = 0.0018). Symptom patterns were similar except bloating was more prevalent in GBT positive and gas in culture positive subjects. CONCLUSIONS & INFERENCES: Duodenal aspiration/culture identifies 45% of patients with suspected SIBO. GBT has lower sensitivity but good specificity for detection of SIBO. There were no ethnic or gender differences in the prevalence of SIBO, but patients with SIBO were older. Because GBT is non-invasive, it should be considered first in patients with suspected SIBO.

Dilute acid pretreatment and enzymatic hydrolysis of sorghum biomass for sugar recovery--a statistical approach.

Sorghum is one of the commercially feasible lignocellulosic biomass and has a great potential of being sustainable feedstock for renewable energy. As with any lignocellulosic biomass, sorghum also requires pretreatment which increases its susceptibility to hydrolysis by enzymes for generating sugars which can be further fermented to alcohol. In the present study, sorghum biomass was evaluated for deriving maximum fermentable sugars by optimizing various pretreatment parameters using statistical optimization methods. Pretreatment studies were done with H2SO4, followed by enzymatic saccharification. The efficiency of the process was evaluated on the basis of production of the total reducing sugars released during the process. Compositional analysis was done for native as well as pretreated biomass and compared. The biomass pretreated with the optimized conditions could yield 0.408 g of reducing sugars /g of pretreated biomass upon enzymatic hydrolysis. The cellulose content in the solid portion obtained after pretreatment using optimised conditions was found to be increased by 43.37% with lesser production of inhibitors in acid pretreated liquor.