Forward-reverse mutation cycles in cancer cell lines under chemical treatments.

Spontaneous forward-reverse mutations were reported by us earlier in clinical samples from various types of cancers and in HeLa cells under normal culture conditions. To investigate the effects of chemical stimulations on such mutation cycles, the present study examined single nucleotide variations (SNVs) and copy number variations (CNVs) in HeLa and A549 cells exposed to wogonin-containing or acidic medium. In wogonin, both cell lines showed a mutation cycle during days 16-18. In acidic medium, both cell lines displayed multiple mutation cycles of different magnitudes. Genomic feature colocalization analysis suggests that CNVs tend to occur in expanded and unstable regions, and near promoters, histones, and non-coding transcription sites. Moreover, phenotypic variations in cell morphology occurred during the forward-reverse mutation cycles under both types of chemical treatments. In conclusion, chemical stresses imposed by wogonin or acidity promoted cyclic forward-reverse mutations in both HeLa and A549 cells to different extents.

Lipoprotein(a) and diet: consuming sugar-sweetened beverages lowers lipoprotein(a) levels in obese and overweight adults.

Lipoprotein(a) [Lp(a)] contributes to cardiovascular disease risk. A genetically determined size polymorphism in apolipoprotein(a) [apo(a)], determined by the number of Kringle (K) repeats, inversely regulates Lp(a) levels. Nongenetic factors including dietary saturated fat influence Lp(a) levels. However, less is known about the effects of carbohydrates including dietary sugars. In this double-blind, parallel arm study among 32 overweight/obese adults, we investigated the effect of consuming glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks on Lp(a) level and assessed the role of the apo(a) size polymorphism. The mean (±SD) age of participants was 54 ± 8 years, 50% were women, and 75% were of European descent. Following the 10-week intervention, Lp(a) level was reduced by an average (±SEM) of -13.2% ± 4.3% in all participants (P = 0.005); -15.3% ± 7.8% in the 15 participants who consumed glucose (P = 0.07); and -11.3% ± 4.5% in the 17 participants who consumed fructose (P = 0.02), without any significant difference in the effect between the two sugar groups. Relative changes in Lp(a) levels were similar across subgroups of lower versus higher baseline Lp(a) level or carrier versus noncarrier of an atherogenic small (≤22K) apo(a) size. In contrast, LDL-C increased. In conclusion, in older, overweight/obese adults, consuming sugar-sweetened beverages reduced Lp(a) levels by ∼13% independently of apo(a) size variability and the type of sugar consumed. The Lp(a) response was opposite to that of LDL-C and triglyceride concentrations. These findings suggest that metabolic pathways might impact Lp(a) levels.

Water bead injuries by children presenting to emergency departments 2013-2023: An expanding issue.

A 2023 product recall has described the risk for morbidity and mortality for children ingesting water beads. We aimed to describe water bead exposure and management trends in the United States. We used the National Electronic Injury Surveillance System (NEISS) to identify water bead injuries from 2013 to 2023. Inclusion criteria were ages 0-17 years, diagnosis of ingested object/foreign body, and the narrative word(s) suggested water bead(s). NEISS supplied weights and variance variables to generate national estimates. There were 226 water bead injuries (66% ingestion). Children under age 2 years comprised 29% of injuries. Multiple water beads were involved in 56% of cases. There was a significant uptrend in water bead injury frequency after 2020. Sixteen (7%) cases required escalation of care. Water bead injuries are rising and appear to affect children of all ages. Children aged less than 5 years appear most vulnerable.

Utility of common bile duct measurement in the diagnosis of cholecystitis and choledocholithiasis in children.

BACKGROUND: Ultrasound is an integral part of evaluating for acute cholecystitis and choledocholithiasis in pediatric patients. Finding the common bile duct (CBD), a structure which is normally <4 mm in children, can be very challenging. OBJECTIVE: The primary objective of this study was to determine the prevalence of isolated sonographic CBD dilation in pediatric patients with acute cholecystitis and/or choledocholithiasis without laboratory abnormalities or pathologic findings on radiology based biliary ultrasound, apart from cholelithiasis. METHODS: We conducted a retrospective chart review of patients ≤21-years-old, at a single free-standing tertiary care children's hospital, who received a biliary ultrasound in the radiology department (RADUS) from September 2005 to February 2020. We identified patients who had a diagnosis of acute cholecystitis and/or choledocholithiasis on RADUS. Based on prior studies, a positive ultrasound was defined as having gallbladder wall thickening (GWT), pericholecystic fluid (PCF), or sonographic Murphy's sign (SMS). The final diagnosis was confirmed using the gold standard, cholecystectomy pathology diagnosis for patients with cholecystitis and endoscopic retrograde cholangiopancreatography (ERCP) diagnosis for patients with choledocholithiasis. Ultrasound data and contemporaneous laboratory values were collected. RESULTS: 180 patients met inclusion criteria. For the study population, 97 (53.9%) had a positive ultrasound, 127 patients (70.6%) had a dilated CBD, and 170 (94.4%) had at least one abnormal laboratory finding. Within the study population there were 76 patients (42.3%) with acute cholecystitis, 55 patients (30.5%) with choledocholithiasis, and 49 patients (27.2%) with acute cholecystitis and choledocholithiasis. Of the 127 patients with a dilated CBD, 80 (62.9%) had a normal ultrasound, apart from cholelithiasis. In this group of 80, 78 patients (97.5%) had at least one abnormal laboratory finding. Thus, for the entire study population, isolated CBD dilation without a positive ultrasound or laboratory abnormalities occurred in 2 patients (1.1%). Of note, these 2 patients had an ultrasound diagnosis of choledocholithiasis. CONCLUSION: The prevalence of isolated sonographic CBD dilation in pediatric patients with cholecystitis and/or choledocholithiasis was 1.1%. Thus, biliary ultrasound without CBD measurement is unlikely to result in missed cholecystitis and/or choledocholithiasis if the biliary ultrasound does not demonstrate GWT, PCF, SMS, or choledocholithiasis, and the patient has normal laboratory values.

Identifying knowledge deficiencies in genetics education among medical students and interns in Saudi Arabia- A cross-sectional study.

BACKGROUND: Understanding genetics is crucial for medical students, particularly in Saudi Arabia, where genetic disorders are prevalent owing to high rates of consanguineous marriages. This knowledge is essential for the early detection, prevention, and management of genetic disorders, and for incorporating medical genetics and genomics into patient care. This study aimed to assess the current state of genetics knowledge among medical students and interns across Saudi Arabia and to identify knowledge gaps in genetics. METHOD: A cross-sectional study was conducted between August and September 2023 involving 732 medical students from all regions of Saudi Arabia. The participants completed a validated questionnaire assessing their knowledge of basic genetics, genetic inheritance, genetic testing, and clinical genetics. RESULT: Over 60% of medical students and interns reported that they considered themselves to have only slight knowledge in all areas of genetics. The results revealed a general lack of medical genetic understanding among students and interns, particularly regarding genetic inheritance and testing. For genetic inheritance, slight knowledge was found in 65.2% of pre-clinical, 60.1% of clinical, and 53.2% of interns, with significant differences between groups (p < 0.001). In genetic testing, 75.4% of pre-clinical, 83.9% of clinical, and 90.6% of interns showed slight knowledge, with significant differences across stages (p = 0.021). This study also found that lectures, genetics laboratories, and problem-solving sessions were the preferred resources for learning genetics. CONCLUSION: The current study revealed a notable deficiency in the understanding of medical genetics among medical students and interns in Saudi Arabia, particularly regarding genetic inheritance and testing. This is consistent with previous research highlighting the widespread lack of genetics knowledge among medical students. Integrating more comprehensive genetics education, especially during the clinical years, could improve students' preparedness and confidence in managing genetic disorders. These findings highlight the critical need for curriculum development to equip future physicians with the essential skills for managing genetic disorders.

Reducing saturated fat intake lowers LDL-C but increases Lp(a) levels in African Americans: the GET-READI feeding trial.

Reducing dietary saturated fatty acids (SFA) intake results in a clinically significant lowering of low-density lipoprotein cholesterol (LDL-C) across ethnicities. In contrast, dietary SFA's role in modulating emerging cardiovascular risk factors in different ethnicities remains poorly understood. Elevated levels of lipoprotein(a) [Lp(a)], an independent cardiovascular risk factor, disproportionally affect individuals of African descent. Here, we assessed the responses in Lp(a) levels to dietary SFA reduction in 166 African Americans enrolled in GET-READI (The Gene-Environment Trial on Response in African Americans to Dietary Intervention), a randomized controlled feeding trial. Participants were fed two diets in random order for 5 weeks each: 1) an average American diet (AAD) (37% total fat: 16% SFA), and 2) a diet similar to the Dietary Approaches to Stop Hypertension (DASH) diet (25% total fat: 6% SFA). The participants' mean age was 35 years, 70% were women, the mean BMI was 28 kg/m2, and the mean LDL-C was 116 mg/dl. Compared to the AAD diet, LDL-C was reduced by the DASH-type diet (mean change: -12 mg/dl) as were total cholesterol (-16 mg/dl), HDL-C (-5 mg/dl), apoA-1 (-9 mg/dl) and apoB-100 (-5 mg/dl) (all P < 0.0001). In contrast, Lp(a) levels increased following the DASH-type diet compared with AAD (median: 58 vs. 44 mg/dl, P < 0.0001). In conclusion, in a large cohort of African Americans, reductions in SFA intake significantly increased Lp(a) levels while reducing LDL-C. Future studies are warranted to elucidate the mechanism(s) underlying the SFA reduction-induced increase in Lp(a) levels and its role in cardiovascular risk across populations.

HLA-B*27 and Ankylosing Spondylitis: 50 Years of Insights and Discoveries.

PURPOSE OF REVIEW: To commemorate the 50th anniversary of the groundbreaking discovery of a remarkably strong association between HLA-B*27 and ankylosing spondylitis (AS). RECENT FINDINGS: In addition to HLA-B*27, more than 116 other recognized genetic risk variants have been identified, while epigenetic factors largely remain unexplored in this context. Among patients with AS who carry the HLA-B*27 gene, clonally expanded CD8 + T cells can be found in their bloodstream and within inflamed tissues. Moreover, the α and ß chain motifs of these T-cell receptors demonstrate a distinct affinity for certain self- and microbial-derived peptides, leading to an autoimmune response that ultimately results in the onset of the disease. These distinctive peptide-binding and presentation characteristics are a hallmark of the disease-associated HLA-B*27:05 subtype but are absent in HLA-B*27:09, a subtype not associated with the disease, differing by only a single amino acid. This discovery represents a significant advancement in unraveling the 50-year-old puzzle of how HLA-B*27 contributes to the development of AS. These findings will significantly accelerate the process of identifying peptides, both self- and microbial-derived, that instigate autoimmunity. This, in return, will pave the way for the development of more accurate and effective targeted treatments. Moreover, the discovery of improved biomarkers, in conjunction with the emerging technology of electric field molecular fingerprinting, has the potential to greatly bolster early diagnosis capabilities. A very recently published groundbreak paper underscores the remarkable effectiveness of targeting and eliminating disease-causing T cells in a HLA-B*27 patients with AS. This pivotal advancement not only signifies a paradigm shift but also bolsters the potential for preventing the disease in individuals carrying high-risk genetic variants.

On the 12C2H2 near-infrared spectrum: absolute transition frequencies and an improved spectroscopic network at the kHz accuracy level.

Lamb dips of twenty lines in the P, Q, and R branches of the ν1 + ν3 + ν41 vibrational band of 12C2H2, in the spectral window of 7125-7230 cm-1, have been measured using an upgraded comb-calibrated frequency-stabilized cavity ring-down spectrometer, designed for extensive sub-Doppler measurements. Due to the large number of carefully executed Lamb-dip experiments, and to the extrapolation of absolute frequencies to zero pressure in each case, the combined average uncertainty of the measured line-center positions is 15 kHz (5 × 10-7 cm-1) with a 2-σ confidence level. Selection of the twenty lines was based on the theory of spectroscopic networks (SN), ensuring that a large number of transitions, measured previously by precision-spectroscopy investigations, could be connected to the para and ortho principal components of the SN of 12C2H2. The assembled SN contains 331 highly precise transitions, 119 and 121 of which are in the ortho and para principal components, respectively, while the rest remain in floating components. The para- and ortho-12C2H2 energy-level lists, determined during the present study, contain 82 and 80 entries, respectively, with an accuracy similar to that of the lines. Based on the newly assembled lists of para- and ortho-12C2H2 empirical energy levels, a line list, called TenkHz, has been generated. The TenkHz line list contains 282 entries in the spectral range of 5898.97-7258.87 cm-1; thus far, only 149 of them have been measured directly via precision spectroscopy. The TenkHz line list includes 35 intense lines that are missing in the HITRAN2020 database.

A single-center experience of post-transplant atypical hemolytic uremic syndrome.

PURPOSE: Atypical hemolytic uremic syndrome (aHUS) is a genetic-based thrombotic microangiopathy (TMA) that is mediated by the activation of the alternative complement pathway. Heterozygous deletion in CFHR3-CFHR1 occurs in 30% of the general population and has not been classically linked to aHUS. Post-transplant aHUS has been associated with a high rate of graft loss. Herein, we report our case series of patients who developed aHUS after solid-organ transplantation. MATERIALS AND METHODS: Five consecutive cases of post-transplant aHUS were identified at our center. Genetic testing was performed in all but one. RESULTS: One patient had a presumed TMA diagnosis before transplant. One heart and 4 kidney (KTx) transplant recipients were diagnosed with aHUS based on the clinical picture of TMA, acute kidney injury, and normal ADAMTS13 activity. Genetic mutation testing revealed heterozygous deletion in CFHR3-CFHR1 in 2 patients and a heterozygous complement factor I (CFI) variant of uncertain clinical significance (VUCS) (Ile416Leu) in a third. Four patients were on tacrolimus, 1 had anti-HLA-A68 donor-specific antibody (DSA), and another had borderline acute cellular rejection at the time of aHUS diagnosis. Four responded to eculizumab, and 1 out of 2 patients came off renal replacement therapy. One KTx recipient died from severe bowel necrosis in the setting of early post-transplant aHUS. CONCLUSION: Calcineurin inhibitors, rejection, DSA, infections, surgery, and ischemia-reperfusion injury are common triggers that could unmask aHUS in solid-organ transplant recipients. Heterozygous deletion in CFHR3-CFHR1 and CFI VUCS may be important susceptibility factors acting as the first hit for alternative complement pathway dysregulation.

JAK Inhibitors for Axial Spondyloarthritis: What does the Future Hold?

PURPOSE OF REVIEW: To discuss the potential role of JAK inhibitors (JAKis) as a new therapeutic class for the treatment of axial spondyloarthritis (axSpA, including ankylosing spondylitis [AS] and non-radiographic axSpA [nr-axSpA]). RECENT FINDINGS: A phase III randomized controlled trial of tofacitinib (a "pan JAKi") in patients with active AS was found to be superior to placebo in achieving the ASAS20 primary endpoint at week 16 (56.4% and 29.4%, p < 0.0001, phase II trials of AS). Upadacitinib, a JAK1 inhibitor, has also been evaluated in a phase III trial for its efficacy and safety in AS. The primary endpoint, ASAS40 at week 16, was reached by 52% of the patients randomized to upadacitinib and 26% of the patients receiving placebo (p = 0·0003). All the important secondary endpoints also improved with both agents. No new changes in their safety profile were noted. However, the more frequent occurrence of cardiovascular and cancer adverse events associated with tofacitinib than with TNFi observed in the very recent post-marketing "ORAL surveillance" safety study, the results of which were released on January 27, 2021, may lead to safety concerns swirling around the whole class of JAKis. JAKis seem to be effective in treating signs and symptoms of AS but have not been studied in nr-axSpA. Both tofacitinib and upadacitinib have been pre-registered with the FDA for the treatment of AS. Upadacitinib has just recently received approval for this indication in the European Union..

"A banana a day keeps wound failure away": comparing the utility of fruit, pig, and synthetic skins for suturing practice.

OBJECTIVES: To investigate how suturing orange and banana peels, pig skin, and synthetic skin compares with the experience of suturing human skin. DESIGN: Interventional study of simple interrupted, vertical mattress, and subcuticular suturing on the four test materials. PARTICIPANTS, SETTING: Fifteen consultants and six trainees in surgical and emergency medicine specialties at a New South Wales regional teaching hospital. MAIN OUTCOME MEASURES: The primary outcome was completion of simple interrupted, vertical mattress, and subcutaneous sutures. Secondary outcomes (assessed in a questionnaire) were similarity of suturing each material to suturing human skin, suitability of each material for practising each suture type, and similarity of each material to human anatomic skin types. RESULTS: All 21 participants completed simple interrupted sutures in bananas and pig and synthetic skins, and 15 in orange skin (P = 0.002). All 21 participants completed vertical mattress sutures in pig and synthetic skins, 18 in bananas, and six in oranges (P < 0.001). The numbers of completed subcuticular sutures were lower for the two fruits (orange, zero; banana, two) than for pig and synthetic skins (each, 21; P < 0.001). Banana peel was rated as somewhat similar to human skin and recommended for practising simple interrupted and vertical mattress suturing. CONCLUSIONS: Bananas are not only useful as healthy snacks between theatre cases, but also for practising and improving simple and vertical mattress suturing skills. However, less portable and nourishing materials are required for subcuticular suturing practice, such as pig skin or synthetic skin.

Review of Current Guided Wave Ultrasonic Testing (GWUT) Limitations and Future Directions.

Damage is an inevitable occurrence in metallic structures and when unchecked could result in a catastrophic breakdown of structural assets. Non-destructive evaluation (NDE) is adopted in industries for assessment and health inspection of structural assets. Prominent among the NDE techniques is guided wave ultrasonic testing (GWUT). This method is cost-effective and possesses an enormous capability for long-range inspection of corroded structures, detection of sundries of crack and other metallic damage structures at low frequency and energy attenuation. However, the parametric features of the GWUT are affected by structural and environmental operating conditions and result in masking damage signal. Most studies focused on identifying individual damage under varying conditions while combined damage phenomena can coexist in structure and hasten its deterioration. Hence, it is an impending task to study the effect of combined damage on a structure under varying conditions and correlate it with GWUT parametric features. In this respect, this work reviewed the literature on UGWs, damage inspection, severity, temperature influence on the guided wave and parametric characteristics of the inspecting wave. The review is limited to the piezoelectric transduction unit. It was keenly observed that no significant work had been done to correlate the parametric feature of GWUT with combined damage effect under varying conditions. It is therefore proposed to investigate this impending task.

The novel function of the Ph1 gene to differentiate homologs from homoeologs evolved in Triticum turgidum ssp. dicoccoides via a dramatic meiosis-specific increase in the expression of the 5B copy of the C-Ph1 gene.

The Ph1 gene is the principal regulator of homoeologous chromosome pairing control (HECP) that ensures the diploid-like meiotic chromosome pairing behavior of polyploid wheat. The HECP control was speculated to have evolved after the first event of polyploidization. With the objective to accurately understand the evolution of the HECP control, wild emmer wheat accessions previously known to differ for HECP control were characterized for the structure and expression of the candidate Ph1 gene, C-Ph1. The C-TdPh1-5A and 5B gene copies of emmer wheat showed 98 and 99% DNA sequence similarity respectively with the corresponding hexaploid wheat copies. Further, the C-TdPh1-5B carried the C-Ph1-5B specific structural changes and transcribed three splice variants as observed in the hexaploid wheat. Further, single nucleotide changes differentiating accessions varying for HECP control were identified. Analyzed by quantitative expression analysis, the wild emmer accessions with HECP control showed ~ 10,000-fold higher transcript abundance of the C-TdPh1-5B copy during prophase-I compared to accessions lacking the control. Differential transcriptional regulation of C-TdPh1-5B splice variants further revealed that C-Ph1-5Balt1 variant is mainly responsible for differential accumulation of C-Ph1-5B copy in accessions with HECP control. Taken together, these results showed that the HECP control evolved via transcriptional regulation of splice variants during meiosis.

A universal drug delivery catheter for the treatment of infrapopliteal arterial disease using liquid therapy.

OBJECTIVE: The objective of this study was to investigate the safety and feasibility of treating infrapopliteal lesions using a novel drug delivery catheter locally delivering liquid paclitaxel. BACKGROUND: Balloon angioplasty is currently the Gold Standard to treat below-the-knee disease; however, restenosis continues to be a great challenge following these percutaneous revascularization procedures. METHODS: The Occlusion Perfusion Catheter for Optimal Delivery of Paclitaxel for the Prevention of Endovascular Restenosis (COPPER-A) study-Below-the-Knee Cohort was a prospective, nonrandomized, multicenter, feasibility, and safety study that enrolled 35 patients at 11 participating sites. The safety endpoints at 1, 3, and 6 months were freedom from thrombosis, major amputation in the target limb and target limb related death. The efficacy endpoints were primary patency and freedom from clinically driven target lesion revascularization at 6 months. RESULTS: All patients tolerated the procedure well with no reports of adverse procedural events. Thirty-five patients were treated with a mean lesion length of 112 ± 81.2 mm with the lesion length range of 20-286 mm. At 6-month follow-up, primary patency was 89.3% and freedom from clinically driven target lesion revascularization was 96.4%. No patients demonstrated thrombosis, major amputation in the target limb and target limb related death at the 1-, 3- and 6-months follow-up intervals. CONCLUSIONS: The results of this multi-center study demonstrated that infrapopliteal arteries can be safely and effectively treated with liquid paclitaxel using the occlusion perfusion catheter.

In Situ and Real-Time Monitoring of Nanoparticle Formation in Microemulsion by Means of Dielectric Spectroscopy.

Dielectric spectroscopy was employed, for the first time, to monitor the formation process of silica nanoparticles in a nonionic surfactant-based microemulsion in situ and in real time. Two dominant relaxations were observed in the frequency range of 1 MHz-3 GHz during this process. The relaxation at the lower frequency range was confirmed to be mainly ascribed to interfacial polarization, whose relaxation parameters, together with the electrical property of the synthesis system, were used to characterize the evolution of this dynamic formation process. Four evolution stages are distinctively revealed, including an induction stage, a nucleation dominant stage, an early particle growth stage, and a late growth stage. The dynamic features at each evolution stages were discussed in terms of the dielectric characteristics of the system. It is strongly suggested that dielectric spectroscopy is an effective tool for the in situ mechanistic study of nanoparticle formation in microemulsion.

Is Axial Spondyloarthritis More Common Than Rheumatoid Arthritis?

PURPOSE OF REVIEW: To discuss the disease incidence and prevalence rates of axial spondyloarthritis (axSpA) and ankylosing spondylitis (AS) relative to those of rheumatoid arthritis (RA). RECENT FINDINGS: According to the most recently published systematic reviews, pooled prevalence estimates for RA are 0.38% in North America, and 0.21 to 0.25% in European subregions, while that of AS is 0.20% in North America and 0.25% in Europe. The estimated prevalence of axSpA has been reported to be approximately twice as common as AS in a study from the USA. This finding has also been supported by studies from northern Norway, central Italy, western Turkey, northern and southern regions of China, and rural Taiwan. These data suggest that axSpA, that encompasses AS, may be more prevalent than RA, at least in some countries. In general, higher occurrences of RA relative to AS have been noted worldwide, both in terms of incidence and prevalence. But axSpA, that encompasses AS, may be more prevalent than RA, at least in some countries. There is a need for concurrently run studies in the same population for a reliable comparison to establish occurrence of RA, AS, and axSpA. It is hoped that the implementation of the ICD-11 codes for axSpA will be helpful in determining a more accurate estimate of its incidence and prevalence.

A Machine Learning Approach to Model Interdependencies between Dynamic Response and Crack Propagation.

Accurate damage detection in engineering structures is a critical part of structural health monitoring. A variety of non-destructive inspection methods has been employed to detect the presence and severity of the damage. In this research, machine learning (ML) algorithms are used to assess the dynamic response of the system. It can predict the damage severity, damage location, and fundamental behaviour of the system. Fatigue damage data of aluminium and ABS under coupled mechanical loads at different temperatures are used to train the model. The model shows that natural frequency and temperature appear to be the most important predictive features for aluminium. It appears to be dominated by natural frequency and tip amplitude for ABS. The results also show that the position of the crack along the specimen appears to be of little importance for either material, allowing simultaneous prediction of location and damage severity.

Inpatient Outcomes for Gastrointestinal Bleeding Associated With Percutaneous Coronary Intervention.

GOALS: The goal of this study was to evaluate the impact of inpatient outcomes of gastrointestinal bleeding (GIB) related to percutaneous coronary intervention (PCI). BACKGROUND: With all-cause mortality increasing in patients undergoing PCIs, outcomes for GIB associated with PCI may be adversely impacted. STUDY: Using the National Inpatient Sample (2007 to 2012), we performed a nested case-control study assessing inpatient outcomes including incidence and mortality for PCI-related GIB hospitalizations. Multivariate logistic regression analyses were performed to determine significant predictors for GIB incidence and mortality. RESULTS: A total of 9332 (1.2%) of PCI hospitalizations were complicated by GIB with the age-adjusted incidence rate increasing 13% from 2007 (11.3 GIB per 1000 PCI) to 2012 (12.8). Patients ≥75 years of age experienced the steepest incline in GIB incidence, which increased 31% during the study period. Compared with non-GIB patients, mean length of stay (9.4 d vs. 3.3 d) and median cost of care ($29,236 vs. $17,913) was significantly higher. Significant demographic risk factors for GIB included older age and comorbid risk factors included gastritis or duodenitis, and Helicobacter pylori infection.In total, 1044 (11%) of GIB patients died during hospitalization with the GIB mortality rate increasing 30% from 2007 (95 deaths per 1000 GIB) to 2012 (123). Older age had the strongest association with inpatient mortality. CONCLUSIONS: Inpatient incidence and mortality for PCI-related GIB has been increasing particularly with a large increase in incidence among older patients. A multidisciplinary approach focused on risk-stratifying patients may improve preventable causes of GIB.

Trends in Incidence and Outcomes of Clostridium difficile Colitis in Hospitalized Patients of Febrile Neutropenia: A Nationwide Analysis.

INTRODUCTION: Clostridium difficile infection (CDI) has been attracting attention lately as the most common hospital acquired infection. Patients with neutropenia because of malignancy seem to be at an increased risk for developing CDI. There is currently limited data that assesses the national burden and outcomes of CDI in Febrile Neutropenia (FN). METHODS: We analyzed the National Inpatient Sample (NIS) database for all subjects with discharge diagnosis of FN with or without CDI (ICD-9 codes 288.00, 288.03,780.60, and 008.45) as primary or secondary diagnosis during the period from 2008 to 2014. All analyses were performed with SAS, version 9.4 (SAS Institute). RESULTS: From 2008 to 2014 there were total 19422 discharges of FN patients with CDI. There was a rising incidence of CDI in patients with FN from 4.11% (in 2008) to 5.83% (in 2014). The In-hospital mortality showed a decreasing trend from 7.79% (in 2008) to 5.32% (in 2014), likely because of improvements in diagnostics and treatment. The overall mortality (6.37% vs. 4.61%), length of stay >5 days (76.45% vs. 50.98%), hospital charges >50,000 dollars (64.43% vs. 40.29%), colectomy and colostomy (0.35% vs. 0.15%), and discharge to skilled nursing facility (10.47% vs. 6.43%) was significantly more in FN patients with CDI versus without CDI over 7 years (2008 to 2014). Age above 65 years, Hispanic race, hematological malignancies, urban hospital settings, and sepsis were significant predictors of mortality in febrile neutropenia patients with CDI. DISCUSSION: Despite the significant decrease in mortality, the incidence of CDI is rising in hospitalized FN patients with underlying hematological malignancies. Risk factor modification, with the best possible empiric antibiotic regimen is imperative for reducing mortality and health care costs in this cohort.

Is prolonged cold ischemia a contraindication to using kidneys from acute kidney injury donors?

To determine the impact of prolonged cold ischemia time (CIT) on the outcome of acute kidney injury (AKI) renal grafts, we therefore performed a single-center retrospective analysis in adult patients receiving kidney transplantation (KT) from AKI donors. Outcomes were stratified according to duration of CIT. A total of 118 patients receiving AKI grafts were enrolled. Based on CIT, patients were stratified as follows: (i) <20 hours, 27 patients; (ii) 20-30 hours, 52 patients; (iii) 30-40 hours, 30 patients; (iv) ≥40 hours, nine patients. The overall incidence of delayed graft function DGF was 41.5%. According to increasing CIT category, DGF rates were 30%, 42%, 40%, and 78%, respectively (P = .03). With a mean follow-up of 48 months, overall patient and graft survival rates were 91% and 81%. Death-censored graft survival (DCGS) rates were 84% and 88% for patients with and without DGF (P = NS). DCGS rates were 92% in patients with CIT <20 hours compared to 85% with CIT >20 hours (P = NS). In the nine patients with CIT >40 hours, the 4-year DCGS rate was 100%. We conclude that prolonged CIT in AKI grafts may not adversely influence outcomes and so discard of AKI kidneys because of projected long CIT is not warranted when donors are wisely triaged.