Global 30-day morbidity and mortality of surgery for perforated peptic ulcer: GRACE study.

BACKGROUND: There is little international data on morbidity and mortality of surgery for perforated peptic ulcer (PPU). This study aimed to understand the global 30-day morbidity and mortality of patients undergoing surgery for PPU and to identify variables associated with these. METHOD: We performed an international study of adults (≥ 18 years) who underwent surgery for PPU from 1st January 2022 to 30th June 2022. Patients who were treated conservatively or had an underlying gastric cancer were excluded. Patients were divided into subgroups according to age (≤ 50 and > 50 years) and time from onset of symptoms to hospital presentation (≤ 24 and > 24 h). Univariate and Multivariate analyses were carried out to identify factors associated with higher 30-day morbidity and mortality. RESULTS:  1874 patients from 159 centres across 52 countries were included. 78.3% (n = 1467) of the patients were males and the median (IQR) age was 49 years (25). Thirty-day morbidity and mortality were 48.5% (n = 910) and 9.3% (n = 174) respectively. Median (IQR) hospital stay was 7 (5) days. Open surgery was performed in 80% (n = 1505) of the cohort. Age > 50 years [(OR = 1.7, 95% CI 1.4-2), (OR = 4.7, 95% CI 3.1-7.6)], female gender [(OR = 1.8, 95% CI 1.4-2.3), (OR = 1.9, 95% CI 1.3-2.9)], shock on admission [(OR = 2.1, 95% CI 1.7-2.7), (OR = 4.8, 95% CI 3.2-7.1)], and acute kidney injury [(OR = 2.5, 95% CI 1.9-3.2), (OR = 3.9), 95% CI 2.7-5.6)] were associated with both 30-day morbidity and mortality. Delayed presentation was associated with 30-day morbidity [OR = 1.3, 95% CI 1.1-1.6], but not mortality. CONCLUSIONS: This study showed that surgery for PPU was associated with high 30-day morbidity and mortality rate. Age, female gender, and signs of shock at presentation were associated with both 30-day morbidity and mortality.

Electronic Health Records (EHRs) Can Identify Patients at High Risk of Fracture but Require Substantial Race Adjustments to Currently Available Fracture Risk Calculators.

BACKGROUND: Osteoporotic fracture prediction calculators are poorly utilized in primary care, leading to underdiagnosis and undertreatment of those at risk for fracture. The use of these calculators could be improved if predictions were automated using the electronic health record (EHR). However, this approach is not well validated in multi-ethnic populations, and it is not clear if the adjustments for race or ethnicity made by calculators are appropriate. OBJECTIVE: To investigate EHR-generated fracture predictions in a multi-ethnic population. DESIGN: Retrospective cohort study using data from the EHR. SETTING: An urban, academic medical center in Philadelphia, PA. PARTICIPANTS: 12,758 White, 7,844 Black, and 3,587 Hispanic patients seeking routine care from 2010 to 2018 with mean 3.8 years follow-up. INTERVENTIONS: None. MEASUREMENTS: FRAX and QFracture, two of the most used fracture prediction tools, were studied. Risk for major osteoporotic fracture (MOF) and hip fracture were calculated using data from the EHR at baseline and compared to the number of fractures that occurred during follow-up. RESULTS: MOF rates varied from 3.2 per 1000 patient-years in Black men to 7.6 in White women. FRAX and QFracture had similar discrimination for MOF prediction (area under the curve, AUC, 0.69 vs. 0.70, p=0.08) and for hip fracture prediction (AUC 0.77 vs 0.79, p=0.21) and were similar by race or ethnicity. FRAX had superior calibration than QFracture (calibration-in-the-large for FRAX 0.97 versus QFracture 2.02). The adjustment factors used in MOF prediction were generally accurate in Black women, but underestimated risk in Black men, Hispanic women, and Hispanic men. LIMITATIONS: Single center design. CONCLUSIONS: Fracture predictions using only EHR inputs can discriminate between high and low risk patients, even in Black and Hispanic patients, and could help primary care physicians identify patients who need screening or treatment. However, further refinements to the calculators may better adjust for race-ethnicity.

BMDs Derived From Total Body DXA are Strongly Correlated With Dedicated Hip and Spine BMD and are Associated With Prior Fractures in NHANES.

Dedicated dual energy X-ray absorptiometry (DXA) bone mineral density (BMD) of the hip and spine are strongly associated with fractures, but it is not clear whether total body (TB) DXA measures correlate with dedicated DXA or relate to fractures. Using National Health and Nutrition Examination Survey (NHANES) data from years 2013-2014 and 2017-2018, we assessed Pearson correlations between dedicated and TB DXA measures. Associations with fractures were examined using self-reported prior fractures or fractures found on vertebral fracture assessment (VFA) using logistic regression models while controlling for age, gender, race/ethnicity, and body mass index. Among 1418 subjects from NHANES 2013-2014, we found signification correlations between all dedicated DXA BMD and TB DXA BMD measures. For dedicated spine BMD, the TB site with the strongest correlation was TB lumbar spine (r = 0.87, p < 0.001), while for dedicated total hip and femoral neck BMD, total body, pelvis, leg, and trunk BMD had the strongest correlations (r = 0.67-0.75, p < 0.001 for all). There were relatively few differences by sex or race/ethnicity. Findings were similar in 481 subjects from NHANES 2017-2018. In NHANES 2013-2014, there were 438 prior fractures in 370 subjects (26.3%). When controlling for age, gender, race/ethnicity, and body mass index, the adjusted odds ratio for fracture per T-score decrease of BMD were similar for TB BMD measures as for dedicated BMD measures (OR 1.10-1.28). In conclusion, total body DXA measures are correlated with hip and spine DXA and are strongly associated with prior fracture. Our results suggest that total body DXA measures are valid alternative sites to study BMD and fracture risk.

Negotiating Gestational Diabetes Mellitus in India: A National Approach.

The worldwide epidemic of diabetes mellitus and hyperglycemia in pregnancy (HIP) presents many challenges, some of which are country-specific. To address these specific problems, parochial resolutions are essential. In India, the government, by working in tandem with (a) national groups such as the Diabetes in Pregnancy Study Group of India, and (b) global organizations such as the International Diabetes Federation, has empowered the medical and paramedical staff throughout the country to manage HIP. Additionally, despite their academic university backgrounds, Indian health planners have provided practical guidelines for caregivers at the ground level, who look up to these experts for guidance. This multipronged process has helped to negotiate some of the multiple problems that are indigenous and exclusive to India. This review traces the Indian journey to manage and prevent HIP with simple, constructive, and pragmatic solutions.

The Prediction of Body Composition in African Americans From Spine and Hip Dual-Energy Absorptiometry.

Body composition, the makeup of the body's fat and lean tissue, is associated with important health outcomes and provides useful clinical information. Although body composition can be measured with total body dual-energy X-ray absorptiometry (DXA), this is rarely performed. As an alternative to total body DXA measurement, methods for estimation of body composition have been developed. These methods use soft tissue measures from spine and hip DXA to predict body composition and include prediction equations previously published by Leslie and proprietary equations within General Electric densitometry software. However, these estimates have not been tested in African Americans (AA), an ethnicity with a different distribution of fat than Caucasians (CA). Therefore, we examined the performance of the existing models in 99 CA and 162 AA subjects over the age of 40 who had total body, spine, and hip DXA measurements. We observed that existing models estimated body composition well in CA but underestimated fat mass and overestimated lean mass in AA. AA subjects were then randomly divided into 2 equal-sized subgroups-the first to develop new prediction equations and the second to independently validate them. We found that body composition can be more accurately estimated using either a new model that we derived in AA subjects using backward stepwise elimination or by adding a fixed offset for AA to the previously published model. Our results demonstrate that body composition estimates from spine and hip DXA require consideration of race/ethnicity.

When are we Going to Settle the Diagnostic Criteria of Gestational Diabetes Mellitus?

Guidelines to diagnose Gestational Diabetes Mellitus (GDM) have changed a number of times from O'Sullivan and Mahan, Carpenter and Coustan, World Health Organization, American Diabetes Association to that of International Association of Diabetes in Pregnancy Study Group (IADPSG). The IADPSG guideline was based on Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study which was performed in caucasian population only and thus literally cannot be considered as international. Recently a study commented that this guideline needs revision for standardization of this strategy for diagnosing GDM. Based on a prospective study, Diabetes in Pregnancy Study Group India (DIPSI) recommended A single step procedure of diagnosing GDM with 2hr PG > 140 mg/dl after 75g of oral glucose administered irrespective of the last meal timing. This guideline has been approved by the Ministry of Health Government of India, WHO, IDF and Federation of Gynaecologists and Obstetricians Society (FIGO). National Institute of Clinical Excellence (NICE) also recognises cut off value, 2hr PG > 140 mg/dl based on a study in multi ethnic population of UK. Hence, we can safely conclude, A Single Step procedure has settled the criteria for diagnosing GDM.

BIS monitoring versus clinical assessment for sedation in mechanically ventilated adults in the intensive care unit and its impact on clinical outcomes and resource utilization.

BACKGROUND: Patients admitted to intensive care and on mechanical ventilation, are administered sedative and analgesic drugs to improve both their comfort and interaction with the ventilator. Optimizing sedation practice may reduce mortality, improve patient comfort and reduce cost. Current practice is to use scales or scores to assess depth of sedation based on clinical criteria such as consciousness, understanding and response to commands. However these are perceived as subjective assessment tools. Bispectral index (BIS) monitors, which are based on the processing of electroencephalographic signals, may overcome the restraints of the sedation scales and provide a more reliable and consistent guidance for the titration of sedation depth.The benefits of BIS monitoring of patients under general anaesthesia for surgical procedures have already been confirmed by another Cochrane review. By undertaking a well-conducted systematic review our aim was to find out if BIS monitoring improves outcomes in mechanically ventilated adult intensive care unit (ICU) patients. OBJECTIVES: To assess the effects of BIS monitoring compared with clinical sedation assessment on ICU length of stay (LOS), duration of mechanical ventilation, any cause mortality, risk of ventilator-associated pneumonia (VAP), risk of adverse events (e.g. self-extubation, unplanned disconnection of indwelling catheters), hospital LOS, amount of sedative agents used, cost, longer-term functional outcomes and quality of life as reported by authors for mechanically ventilated adults in the ICU. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, ProQuest, OpenGrey and SciSearch up to May 2017 and checked references citation searching and contacted study authors to identify additional studies. We searched trial registries, which included clinicaltrials.gov and controlled-trials.com. SELECTION CRITERIA: We included all randomized controlled trials comparing BIS versus clinical assessment (CA) for the management of sedation in mechanically ventilated critically ill adults. DATA COLLECTION AND ANALYSIS: We used Cochrane's standard methodological procedures. We undertook analysis using Revman 5.3 software. MAIN RESULTS: We identified 4245 possible studies from the initial search. Of those studies, four studies (256 participants) met the inclusion criteria. One more study is awaiting classification. Studies were, conducted in single-centre surgical and mixed medical-surgical ICUs. BIS monitor was used to assess the level of sedation in the intervention arm in all the studies. In the control arm, the sedation assessment tools for CA included the Sedation-Agitation Scale (SAS), Ramsay Sedation Scale (RSS) or subjective CA utilizing traditional clinical signs (heart rate, blood pressure, conscious level and pupillary size). Only one study was classified as low risk of bias, the other three studies were classified as high risk.There was no evidence of a difference in one study (N = 50) that measured ICU LOS (Median (Interquartile Range IQR) 8 (4 to 14) in the CA group; 12 (6 to 18) in the BIS group; low-quality evidence).There was little or no effect on the duration of mechanical ventilation (MD -0.02 days (95% CI -0.13 to 0.09; 2 studies; N = 155; I2 = 0%; low-quality evidence)). Adverse events were reported in one study (N = 105) and the effects on restlessness after suction, endotracheal tube resistance, pain tolerance during sedation or delirium after extubation were uncertain due to very low-quality evidence. Clinically relevant adverse events such as self-extubation were not reported in any study. Three studies reported the amount of sedative agents used. We could not measure combined difference in the amount of sedative agents used because of different sedation protocols and sedative agents used in the studies. GRADE quality of evidence was very low. No study reported other secondary outcomes of interest for the review. AUTHORS' CONCLUSIONS: We found insufficient evidence about the effects of BIS monitoring for sedation in critically ill mechanically ventilated adults on clinical outcomes or resource utilization. The findings are uncertain due to the low- and very low-quality evidence derived from a limited number of studies.

Efficacy and Safety of Combined Oral Chelation With Deferiprone and Deferasirox in Children With ß-Thalassemia Major: An Experience From North India.

OBJECTIVE: A combination of desferrioxamine with either deferiprone (DFP) or deferasirox (DFX) for patients with ß-thalassemia major who do not achieve negative iron balance with monotherapy has been studied widely. However, poor compliance resulting from the need for parentral administration of desferrioxamine and its cost necessicitates combining 2 oral chelators. METHODS: A prospective study was conducted in patients with transfusion-dependent ß-thalassemia major in a tertiary care center over 2 years. Patients on either DFP or DFX who were not improving on monotherapy over a long period and persistently maintaining serum ferritin >2500 µg/L were enrolled. Efficacy was assessed by serum ferritin levels assessed at 12 months and 2 years. Complete blood counts and liver and kidney function tests were monitored to assess the safety of the combination of drugs. RESULTS: In total, 33 patients with a mean age of 12.67 years (7.5 to 17.5 y) and a mean ferritin of 4835.2394±1443.85 µg/L formed the study cohort.In total, 28 patients completed the 1-year study period; and 12 patients completed 2 years. Mean serum ferritin reduction at 1 and 2 years was 34.99%±18.13% (range, -34.36% to 56.17%) and 44.67%±13.78% (range, 22.17% to 62.74%), respectively. The combination therapy was well tolerated. CONCLUSIONS: Combined oral chelation with DFP and DFX has better efficacy than either drug used alone. The combination of drugs was well tolerated and no new adverse effects were observed.

Dual-energy X-ray Absorptiometry.

Bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) is the most commonly used method to assess fracture risk. DXA utilizes two different energy X-rays to calculate BMD and, by comparison to a young normative database, the T-score. In 1994, the World Health Organization defined osteoporosis based on T-score, changing the paradigm of the field and forever placing DXA measurements in the center of osteoporosis diagnosis. Since then, many large studies have demonstrated the predictive value of BMD by DXA-for every standard deviation decline in BMD, there is a relative risk of 1.5-2.5 for fracture. This predictive ability is similar to how blood pressure can predict myocardial infarction. Limitations of DXA are also important to consider. While BMD by DXA can identify those at risk, there is a significant overlap in the BMD of patients who will and will not fracture. Special considerations are also needed in men and ethnic minority groups. These groups may have different bone size, thus affecting the normative range of BMD, and/or distinct bone structure that affect the association between BMD and fractures. Finally, BMD can be affected by positioning errors or artifacts, including osteoarthritis, fracture, and jewelry. Of course, DXA has tremendous strengths as well-namely its wide availability, its low radiation exposure, and a large body of evidence that relate DXA measurements to fracture risk. For these reasons, DXA remains the cornerstone of fracture assessment now and for the foreseeable future.

Ethnic Differences in Osteoporosis After Cardiac Transplantation.

Cardiac transplantation is associated with a high risk of fracture. African Americans (AAs) are believed to have a lower risk of osteoporosis than Caucasians, but it is not clear whether they are also protected from osteoporosis resulting from the use of glucocorticoids and/or organ transplantation. We examined possible ethnic differences in 33 cardiac transplant recipients (16 AAs) in a cross-sectional analysis. In addition to bone mineral density and vertebral fracture assessment, we also compared biochemical variables, trabecular bone score, total body dual-energy X-ray absorptiometry, and disability. Overall fracture rates were low in both groups, with only 6 total subjects with fractures on vertebral fracture assessment or history of fracture. While T-scores were similar between groups, Z-scores were lower in AA with the difference reaching statistical significance when controlling for important covariates. The trabecular bone score was also lower in AAs than in Caucasians even when adjusting for age and tissue thickness (1.198 ± 0.140 vs 1.312 ± 0.140, p = 0.03). While AAs are generally thought to be protected from osteoporosis, our study instead suggests that AAs may be at higher risk of bone deterioration after cardiac transplantation and may need to be managed more aggressively than suggested by current guidelines.

Ethnic Differences in Trabecular Bone Score.

Trabecular bone score (TBS), a noninvasive textural analysis of the lumbar spine dual-energy X-ray absorptiometry (DXA) image, has been shown to predict fractures in Caucasian (CA) populations but has not been thoroughly studied in African-American (AA) populations. The aim of this study was to compare the TBS in AAs and CAs and to assess whether TBS can be used to refine fracture risk stratification in AA patients. Eight hundred twenty-five women (390 AAs, 435 CAs) referred for bone mineral density (BMD) as part of their clinical care had measurements of the TBS, the BMD of the lumbar spine, total hip, and femoral neck, and vertebral fracture assessment for detection of vertebral fractures. Unadjusted TBS was higher in CA than AA (1.275 vs 1.238, p < 0.001), but this was no longer true after adjusting for age and tissue thickness. Interestingly, differences in TBS were still highly significant in those under 60 yr of age even with adjustment for tissue thickness, but not in older subjects. There were 74 CAs and 56 AAs with vertebral fractures on vertebral fracture assessment (17% vs 14%, p = 0.30). In CA, the odds ratio (OR) for prevalent vertebral fracture per SD decrease in TBS was 2.33 (p < 0.001), whereas in AA, the OR was 1.43 (p = 0.02). In a multivariate logistic regression model that also included age, BMD T-score, and glucocorticoid use, the association between TBS and prevalent vertebral fractures was still highly significant in CAs (OR 1.54, p = 0.008) but not in AAs (OR 1.23, p = 0.21). Our results suggest that TBS may be less discriminatory in regard to fracture risk in AAs than in CAs and that TBS may need to be used differently in these 2 ethnic groups.

Rapid Discharge to Home After Total Knee Arthroplasty Is Safe in Eligible Medicare Patients.

BACKGROUND: This study was aimed at assessing the risk of readmission for Medicare patients discharged home within a day of total knee arthroplasty (TKA) compared to those discharged on day 2 or beyond in a community medical center. METHODS: A hospital inpatient database was queried for all unilateral, primary TKAs performed on patients 65 years or older from January 1, 2013, to December 31, 2015. A total of 2287 patients met the study criteria, of which 1502 were discharged within a day (short stay), and 785 were discharged on day 2 or beyond (traditional stay). The main outcome measures were all-cause 30-day and unplanned 90-day readmissions. RESULTS: Short-stay patients did not experience a higher 30-day readmission rate (1.1%) compared to the traditional-stay patients (2.7%), nor did they experience a higher rate of unplanned 90-day readmissions (1.7% vs 3.6%). The short-stay group had more favorable demographics compared to the traditional-stay group. Logistic regression results revealed that none of the demographic factors considered had a statistically significant impact on 30-day readmission odds for either group. For unplanned 90-day readmissions, the results showed that for the short-stay patients, with the exception of age, none of the other demographic factors had significant impact on readmission odds and none were significant for the traditional-stay group. CONCLUSION: Our results suggest that the Medicare patients meeting discharge criteria and discharged home within a day of TKA do not have an increased risk of 30-day and 90-day readmission.

The AAHKS Clinical Research Award: Liposomal Bupivacaine and Periarticular Injection Are Not Superior to Single-Shot Intra-articular Injection for Pain Control in Total Knee Arthroplasty.

BACKGROUND: Intraoperative injections can help reduce early postoperative pain in total knee arthroplasty. We proposed that liposomal bupivacaine would not be superior to more common and cheaper injections. METHODS: A single-blinded prospective randomized study with 207 consecutive patients was completed. Patients were randomized to treatment with periarticular liposomal bupivacaine injection, periarticular injection of bupivacaine/morphine, or intra-articular injection of bupivacaine/morphine at the conclusion of the procedure. Postoperative visual analog pain scores and narcotic consumption were recorded and analyzed. RESULTS: There was no significant difference in postoperative visual analog pain scores or narcotic consumption among the 3 study groups. CONCLUSION: Intra-articular injection of bupivacaine and morphine is as effective for postoperative pain control in total knee arthroplasty as periarticular bupivacaine/morphine injection and liposomal bupivacaine. Use of liposomal bupivacaine in total knee arthroplasty is costly and not justified.

Gas-containing Liver Abscess Mimicking Pneumoperitoneum.

Gas under the diaphragm or pneumoperitoneum, is often a sign of grave intra-abdominal pathology. It can be due to either of surgical or non-surgical etiology. Here we present a case of gas under right dome of diaphragm caused by a non-surgical cause i.e. secondary to aspiration of liver abscess.

A Novel Folate-Targeted Nanoliposomal System of Doxorubicin for Cancer Targeting.

Targeted drug delivery systems for cancer improves anti-tumor efficacy and reduces systemic toxicity by restricting availability of cytotoxic drugs within tumors. Targeting moieties, such as natural ligands (folic acid, transferrin, and biotin) which are overexpressed on tumors, have been used to enhance liposome-encapsulated drug accumulation within tumors and resulted in better control. In this report, we explored the scope of targeting ligand folic acid, which is incorporated in liposome systems using folic acid-modified cholesterol (CPF), enabled highly selective tumor-targeted delivery of liposome-encapsulated doxorubicin and resulted in increased cytotoxicity within tumors. Folate-tagged poloxamer-coated liposomes (FDL) were found to have significantly higher cellular uptake than conventional poloxamer-coated liposomes (DL), as confirmed by fluorometric analysis in B16F10 melanoma cells. Biodistribution study of the radiolabeled liposomal system indicated the significantly higher tumor uptake of FDL as compared to DL. Anti-tumor activity of FDL against murine B16F10 melanoma tumor-bearing mice revealed that FDL inhibited tumor growth more efficiently than the DL. Taken together, the results demonstrated the significant potential of the folate-conjugated nanoliposomal system for drug delivery to tumors.

Strategies for improving cardiovascular health in women with diabetes mellitus: a review of the evidence.

Knowledge about cardiovascular (CV) disease in women with diabetes mellitus (DM) has changed substantially over the past 20 years. Coronary artery disease, strokes, and peripheral vascular disease affect women with DM at higher rates than the general population of women. Lifestyle therapies, such as dietary changes, physical activity, and smoking cessation, offer substantial benefits to women with DM. Of the pharmacotherapies, statins offer the most significant benefits but may not be well tolerated in some women. Aspirin may also benefit high-risk women. Other pharmacotherapies, such as fibrates, ezetimibe, niacin, fish oil, and hormone replacement therapy, remain unproven and, in some cases, potentially dangerous to women with DM. To reduce CV events, risks to women with DM must be better publicized and additional research must be done. Finally, advancements in health care delivery must target high-risk women with DM to lower risk factors and effectively improve cardiovascular health.