Prenatal FGFR2 Signaling via PI3K/AKT Specifies the PDGFRA+ Myofibroblast.

It is well known that FGFR2 (fibroblast growth factor receptor 2) signaling is critical for proper lung development. Recent studies demonstrate that epithelial FGFR2 signaling during the saccular phase of lung development (sacculation) regulates alveolar type 1 (AT1) and AT2 cell differentiation. During sacculation, PDGFRA (platelet-derived growth factor receptor-α)-positive lung fibroblasts exist as three functional subtypes: contractile myofibroblasts, extracellular matrix-producing matrix fibroblasts, and lipofibroblasts. All three subtypes are required during alveolarization to establish a niche that supports AT2 epithelial cell self-renewal and AT1 epithelial cell differentiation. FGFR2 signaling directs myofibroblast differentiation in PDGFRA+ fibroblasts during alveolar reseptation after pneumonectomy. However, it remains unknown if FGFR2 signaling regulates PDGFRA+ myo-, matrix, or lipofibroblast differentiation during sacculation. In this study, FGFR2 signaling was inhibited by temporal expression of a secreted dominant-negative FGFR2b (dnFGFR2) by AT2 cells from embryonic day (E) 16.5 to E18.5. Fibroblast and epithelial differentiation were analyzed at E18.5 and postnatal days 7 and 21. At all time points, the number of myofibroblasts was reduced and the number of lipo-/matrix fibroblasts was increased. AT2 cells are increased and AT1 cells are reduced postnatally, but not at E18.5. Similarly, in organoids made with PDGFRA+ fibroblasts from dnFGFR2 lungs, increased AT2 cells and reduced AT1 cells were observed. In vitro treatment of primary wild-type E16.5 adherent saccular lung fibroblasts with recombinant dnFGFR2b/c resulted in reduced myofibroblast contraction. Treatment with the PI3K/AKT activator 740 Y-P rescued the lack of myofibroblast differentiation caused by dnFGFR2b/2c. Moreover, treatment with the PI3K/AKT activator 740 Y-P rescued myofibroblast differentiation in E18.5 fibroblasts isolated from dnFGFR2 lungs.

A phase II study of cabozantinib and pembrolizumab in advanced gastric/gastroesophageal adenocarcinomas resistant or refractory to immune checkpoint inhibitors.

BACKGROUND: Most patients with metastatic gastroesophageal adenocarcinoma (mGEA) progress on immune checkpoint inhibitors (ICIs). Novel approaches to overcome resistance to ICI in mGEA are needed. Cabozantinib is a multi-tyrosine kinase inhibitor thought to enhance the immunomodulatory effects of ICI. This study evaluated the combination of cabozantinib and pembrolizumab in ICI refractory or resistant mGEA. METHODS: Investigator-initiated, single-arm, single institution, and phase II study in patients with mGEA. Patients had progressed on ICI and/or had PD-L1 CPS score ≤10%. Cabozantinib dose was 40 mg p.o. daily on days 1-21 of a 21-day cycle, with pembrolizumab 200 mg i.v. on day 1. The primary endpoint was progression-free survival at 6 months (PFS-6). RESULTS: Twenty-seven patients were enrolled. Median age 58 years (24-87), female (n = 14), ECOG 0/1 = 13/14, GC/GEJ = 16/11, and non-Hispanic White/Hispanic/Asian = 12/8/7. The primary endpoint was met. After a median follow-up of 31.4 months (range 3.3-42.5), PFS-6 was 22.2% (95% CI 9.0-39.0). The median PFS and OS are 2.3 months (95% CI 1.7-4.1) and 5.5 months (3.1-14.0), respectively. The most common mutations were TP53 (78.3%) and CDH1/PIK3CA/CTNNB1 (17.4% each). The most common grade (G) treatment-related adverse events (TRAE) were diarrhea (25.9%), fatigue (18.5%), hypertension, and muscle cramps (14.8% each). G3-4 TRAE were seen in n = 3 patients (hypertension, thromboembolic event, esophageal perforation; each n = 1). No G5 was observed. CONCLUSIONS: The addition of cabozantinib to pembrolizumab shows clinical benefit in ICI-resistant or refractory mGEA with a tolerable safety profile. (ClinicalTrials.gov Identifier: NCT04164979. IRB Approved: UCI 18-124, University of California Irvine IRB#20195426.).

Pneumococcal Serotype-Specific Antibodies in Children with Recurrent Oto-sinopulmonary Infections.

Low titers to pneumococcal vaccine are a frequent finding in pediatric patients with recurrent oto-sinopulmonary infections. To characterize the pre- and post-immunization antibody trend for each serotype included in the pneumococcal 13-valent conjugate vaccine (PCV13), in a cohort of pediatric patients with recurrent oto-sinopulmonary infections. This retrospective review identified 182 patients with recurrent oto-sinopulmonary infections (131 required an immune workup and 99 had low pneumococcal titers leading to a PCV13 vaccine booster). Baseline pneumococcal serotype-specific antibody titers at initial visit and 6 weeks after the vaccine booster were obtained. An adequate response to the pneumococcal conjugate vaccine was deemed to be a 4-fold increase over baseline and/or a post-immunization titer of 1.3 µg/ml or greater. Overall, PCV13 booster provided a significant improvement in the number of protective titers, increasing from 3.6 serotypes at baseline to 11.1 serotypes at 6 weeks (p < 0.001). This increase correlated with improved clinical outcomes (81% showed no signs of recurrent infection after the first booster and 94% after a second booster). Post-immunization antibody concentrations were significantly higher than at baseline for all serotypes (p< 0.05) and only 8, 9N, and 12F did not exhibit a greater than 4-fold increase (p> 0.05) 6 weeks following booster. There were no differences between patients at different ages in post-immunization titer levels for all serotypes. In pediatric patients with recurrent oto-sinopulmonary infections, an additional pneumococcal booster proved to be effective in the protection of these children against further infections, across all age groups.

Randomized controlled multi-centre study comparing shorter dental implants (6 mm) to longer dental implants (11-15 mm) in combination with sinus floor elevation procedures: 10-year data.

AIM: To compare implant survival and complication rates between shorter and standard-length implants with sinus augmentation and restored with single crowns, at 10 years of loading. MATERIALS AND METHODS: One-hundred and one patients (137 implants) with a ridge height of 5-7 mm in the posterior maxilla were randomly assigned to two treatment modalities: shorter implants (6 mm) (group short [GS]) or standard-length implants (11-15 mm) with sinus grafting (group graft [GG]). Following the insertion of final restorations, patients were regularly recalled for up to 10 years. Assessed outcomes encompassed implant survival, marginal bone levels (MBLs), biological and technical parameters and patient-reported outcome measures (OHIP-49 = Oral Health Impact Profile). Non-parametric statistical analysis was used to analyse the data. RESULTS: For the 5- to 10-year follow-up period, 77 patients with 105 implants (GS: 36 patients/48 implants; GG: 41/57) were available for re-examination (drop-out rate 21%). Implant survival rates at the patient level were 96.0% (GS; 2 failures) and 100% (GG) (inter-group p = .24). Median MBLs amounted to 0.00 mm (min 0.00; max 3.25; GS) and 0.00 mm (min 0.00; max 4.55; GG) (inter-group p = .73). Technical complications predominantly occurred within the first 5 years (inter-group p > .05). Peri-implantitis rates were 4.2% (GS) and 13.3% (GG) (intergroup p = .37). Median OHIP-49 scores were 7.00 (0.00; 39.00; GS) and 9.00 (0.00; 196; GG) (inter-group p = .61) at 10 years. CONCLUSIONS: Based on similar 10-year implant survival rates, reduced patient morbidity and lower costs, the use of shorter dental implants might well serve as an alternative treatment concept to longer implants placed in conjunction with sinus grafting for patients with a limited ridge height in the posterior maxilla. Study register: https://clinicaltrials.gov/ct2/show/NCT01030523.

Superhydrophobic coatings reduce human bacterial foodborne pathogen attachment to woods used in fresh produce harvest and postharvest packing.

Wood is reportedly more difficult to maintain in hygienic condition versus other food contact materials, yet its use in produce packing and retail warrants efforts to reduce the risk of microbial pathogen contamination and attachment. This study characterized antifouling capabilities of fluorinated silanes applied to wood used in fresh edible produce handling to render the wood superhydrophobic and less supportive of bacterial pathogen attachment. Pine and oak cubic coupon surfaces were treated with 1% (w/w) silane or left untreated. Treated and untreated coupons were inoculated with Salmonella enterica or Listeria monocytogenes and held to facilitate pathogen attachment for 1, 4, or 8 h. Silane treatment of wood produced significant reductions in the proportions of strongly attaching cells for both pathogens versus loosely attaching cells (P < 0.01). Salmonella attachment demonstrated a dependency on wood treatment; silane-treated wood supported a lower fraction of strongly adhering cells (1.87 ± 1.24 log CFU/cm2) versus untreated wood (3.72 ± 0.67 log CFU/cm2). L. monocytogenes demonstrated significant declines in strongly attaching cells during extended exposure to silane-treated wood, from 7.59 ± 0.14 to 5.27 ± 0.68 log CFU/cm2 over 8 h post-inoculation. Microscopic analysis demonstrated silane treatment increased the surface roughness of both woods, leading to superhydrophobic conditions on wood surfaces, consequently decreasing strong attachment of pathogenic bacteria.

Immunotherapy with CD25/CD71-allodepleted T cells to improve T-cell reconstitution after matched unrelated donor hematopoietic stem cell transplant: a randomized trial.

BACKGROUND AIMS: Delayed immune reconstitution is a major challenge after matched unrelated donor (MUD) stem cell transplant (SCT). In this randomized phase 2 multi-center trial, Adoptive Immunotherapy with CD25/71 allodepleted donor T cells to improve immunity after unrelated donor stem cell transplant (NCT01827579), the authors tested whether allodepleted donor T cells (ADTs) can safely be used to improve immune reconstitution after alemtuzumab-based MUD SCT for hematological malignancies. METHODS: Patients received standard of care or up to three escalating doses of ADTs generated through CD25+/CD71+ immunomagnetic depletion. The primary endpoint of the study was circulating CD3+ T-cell count at 4 months post-SCT. Twenty-one patients were treated, 13 in the ADT arm and eight in the control arm. RESULTS: The authors observed a trend toward improved CD3+ T-cell count at 4 months in the ADT arm versus the control arm (230/µL versus 145/µL, P = 0.18), and three ADT patients achieved normal CD3+ T-cell count at 4 months (>700/µL). The rates of significant graft-versus-host disease (GVHD) were comparable in both cohorts, with grade ≥2 acute GVHD in seven of 13 and four of eight patients and chronic GVHD in three of 13 and three of eight patients in the ADT and control arms, respectively. CONCLUSIONS: These data suggest that adoptive transfer of ADTs is safe, but that in the MUD setting the benefit in terms of T-cell reconstitution is limited. This approach may be of more use in the context of more rigorous T-cell depletion.

Comparison of electronic versus mechanical torque-limiting devices for dental implants: An in vitro study.

PURPOSE: To determine the accuracy of new electronic torque-limiting devices (ET) when compared to new and used conventional-style beam-type (BT) mechanical torque-limiting devices and hand-piece style (HS) mechanical torque-limiting devices. The secondary purpose was to compare any difference in accuracy between new and used mechanical torque-limiting devices, and any difference in accuracy when used on a straight versus an angled screw channel abutment. MATERIALS AND METHODS: A total of five torque-limiting devices were used to obtain 2000 readings under standardized conditions. An implant analog was fastened into a digital torque meter, to which an abutment was connected. Pre-determined torque values of 15 Ncm and 35 Ncm were applied, and actual torque values were recorded. A straight and an angled abutment were used to record 1000 readings each using the five torque-limiting devices. An overall Kruskal-Wallis test was applied to compare the median deviation among devices followed by a pairwise comparison ( = 0.05). RESULTS: For a target torque value of 15 Ncm on a straight abutment, the electronic device (ET) was statistically more accurate than the beam type (BT) new (p < 0.001) and used (p < 0.048) devices but less accurate than the hand-piece style (HS) used device (p < 0.001). On an angled abutment for a target value of 15 Ncm, the electronic device (ET) was statistically more accurate than hand-piece style (HS) new and used devices (p < 0.001). For a target torque value of 35 Ncm on a straight abutment, the ET was statistically more accurate than the HS new device (p < 0.001) but less accurate than the BT new device (p < 0.001). On an angled abutment for a target value of 35 Ncm, the electronic device (ET) was statistically less accurate than the beam-type (BT) new device (p < 0.001), the beam-type (BT) used device (p = 0.001), and the hand-piece style (HS) used device (p < 0.001). The electronic device (ET) was the only device accurate within the ISO standard of accuracy of 6% for each of the target torque value/abutment design combinations. There was no statistically significant difference related to the type of abutment used (angled vs. straight). CONCLUSIONS: Electronic torque limiting devices (ET) are an acceptable method for delivering torque for implant restorations for straight and angled abutments at 15 Ncm and 35 Ncm torque values. Conventional style beam-type (BT) mechanical torque-limiting devices are a simple, predictable, validated, and inexpensive tool for delivering accurate torque at 15 Ncm and 35 Ncm torque values. The hand-piece style (HS) mechanical torque-limiting devices are predictable to deliver 15 Ncm torque values.

A phase Ib feasibility trial of response adapted neoadjuvant therapy in gastric cancer (RANT-GC).

Current guidelines recommend neoadjuvant (NAC) and/or adjuvant chemotherapy for locally advanced gastric cancers (LAGCs). However, the choice and duration of NAC regimen is standardized, rather than personalized to biologic response, despite the availability of several different classes of agents for the treatment of gastric cancer (GC). The current trial will use a tumor-informed ctDNA assay (Signatera™) and monitor response to NAC. Based on ctDNA kinetics, the treatment regimen is modified. This is a prospective single center, single-arm, open-label study in clinical stage IB-III GC. ctDNA is measured at baseline and repeated every 8 weeks. Imaging is performed at the same intervals. The primary end point is the feasibility of this approach, defined as percentage of patients completing gastrectomy.

Leftward and Posterior Deviation of the Septum Primum Predicts Morbidity in Patients with Hypoplastic Left Heart Syndrome.

Leftward posterior deviation of the atrial septum primum (LDSP) has been reported in up to 64% of patients with hypoplastic left heart syndrome (HLHS) but there are no published data on its impact on neonatal outcomes. We reviewed the prevalence of LDSP and its correlation with neonatal outcomes in our institution. This was a single-center retrospective study of neonates with HLHS from 2001 to 2019. Echocardiograms were reviewed and the presence or absence of LDSP was noted. To quantify the degree of deviation in patients with LDSP, a new measurement, the deviation index (DI) was calculated using both the subcostal long and short-axis views. Of ninety-four patients with HLHS, fifty-seven (61%) patients were noted to have LDSP. There was no statistically significant difference in gestational age (GA), birth weight (BW), or mortality between patients with and without LDSP. Patients with LDSP had an increased incidence of unplanned reoperation (p < 0.01), post-operative cardiac catheterization (p < 0.05), and post-operative infection (p < 0.05). After correction for GA, BW, HLHS subtype, and type of surgery, LDSP predicted reoperation (OR = 3.6, p < 0.01), catheterization (OR = 2.7, p = 0.05), and infection (OR = 3.4, p < 0.05). Higher degree of deviation predicted reoperation (DI > 0.17), catheterization (DI > 0.07), and infection (DI > 0.12). There was excellent inter-observer reproducibility of the DI (ICCabsolute-agreement = 0.82, ICCconsistency = 0.90). Patients with LDSP have a higher prevalence of post-operative morbidity. The degree of deviation was found to be predictive of post-operative complications. Pre-operative echocardiographic evaluation of LDSP in patients with HLHS may be helpful in risk stratification and counseling.

Custom Made Device for Removal of Removable Partial Denture in a Patient with Manual Impairment.

Manual impairment could be part of the clinical presentation of a number of systemic conditions or traumas. Inability to successfully remove a removable partial denture is one of the contraindications of this type of treatment. This report presents a technique for fabrication of a custom device made chairside to assist a manually impaired patient due to osteoarthritis with the removal of a removable mandibular prosthesis. This technique could allow patients with similar conditions to replace their missing teeth with removable partial dentures, in cases where a fixed restoration is not an option.

Earlier diagnosis of lung cancer in a randomised trial of an autoantibody blood test followed by imaging.

The EarlyCDT-Lung test is a high-specificity blood-based autoantibody biomarker that could contribute to predicting lung cancer risk. We report on the results of a phase IV biomarker evaluation of whether using the EarlyCDT-Lung test and any subsequent computed tomography (CT) scanning to identify those at high risk of lung cancer reduces the incidence of patients with stage III/IV/unspecified lung cancer at diagnosis compared with the standard clinical practice at the time the study began.The Early Diagnosis of Lung Cancer Scotland (ECLS) trial was a randomised controlled trial of 12 208 participants at risk of developing lung cancer in Scotland in the UK. The intervention arm received the EarlyCDT-Lung test and, if test-positive, low-dose CT scanning 6-monthly for up to 2 years. EarlyCDT-Lung test-negative and control arm participants received standard clinical care. Outcomes were assessed at 2 years post-randomisation using validated data on cancer occurrence, cancer staging, mortality and comorbidities.At 2 years, 127 lung cancers were detected in the study population (1.0%). In the intervention arm, 33 out of 56 (58.9%) lung cancers were diagnosed at stage III/IV compared with 52 out of 71 (73.2%) in the control arm. The hazard ratio for stage III/IV presentation was 0.64 (95% CI 0.41-0.99). There were nonsignificant differences in lung cancer and all-cause mortality after 2 years.ECLS compared EarlyCDT-Lung plus CT screening to standard clinical care (symptomatic presentation) and was not designed to assess the incremental contribution of the EarlyCDT-Lung test. The observation of a stage shift towards earlier-stage lung cancer diagnosis merits further investigations to evaluate whether the EarlyCDT-Lung test adds anything to the emerging standard of low-dose CT.

Protein-polymer mixtures in the colloid limit: Aggregation, sedimentation, and crystallization.

While proteins have been treated as particles with a spherically symmetric interaction, of course in reality, the situation is rather more complex. A simple step toward higher complexity is to treat the proteins as non-spherical particles and that is the approach we pursue here. We investigate the phase behavior of the enhanced green fluorescent protein (eGFP) under the addition of a non-adsorbing polymer, polyethylene glycol. From small angle x-ray scattering, we infer that the eGFP undergoes dimerization and we treat the dimers as spherocylinders with aspect ratio L/D - 1 = 1.05. Despite the complex nature of the proteins, we find that the phase behavior is similar to that of hard spherocylinders with an ideal polymer depletant, exhibiting aggregation and, in a small region of the phase diagram, crystallization. By comparing our measurements of the onset of aggregation with predictions for hard colloids and ideal polymers [S. V. Savenko and M. Dijkstra, J. Chem. Phys. 124, 234902 (2006) and Lo Verso et al., Phys. Rev. E 73, 061407 (2006)], we find good agreement, which suggests that the behavior of the eGFP is consistent with that of hard spherocylinders and ideal polymers.

Recent developments in antimicrobial and antifouling coatings to reduce or prevent contamination and cross-contamination of food contact surfaces by bacteria.

Illness as the result of ingesting bacterially contaminated foodstuffs represents a significant annual loss of human quality of life and economic impact globally. Significant research investment has recently been made in developing new materials that can be used to construct food contacting tools and surfaces that might minimize the risk of cross-contamination of bacteria from one food item to another. This is done to mitigate the spread of bacterial contamination and resultant foodborne illness. Internet-based literature search tools such as Web of Science, Google Scholar, and Scopus were utilized to investigate publishing trends within the last 10 years related to the development of antimicrobial and antifouling surfaces with potential use in food processing applications. Technologies investigated were categorized into four major groups: antimicrobial agent-releasing coatings, contact-based antimicrobial coatings, superhydrophobic antifouling coatings, and repulsion-based antifouling coatings. The advantages for each group and technical challenges remaining before wide-scale implementation were compared. A diverse array of emerging antimicrobial and antifouling technologies were identified, designed to suit a wide range of food contact applications. Although each poses distinct and promising advantages, significant further research investment will likely be required to reliably produce effective materials economically and safely enough to equip large-scale operations such as farms, food processing facilities, and kitchens.

Occlusal Schemes for Implant Restorations: Best Evidence Consensus Statement.

PURPOSE: Numerous studies have focused on the various complications with implant-retained restorations and a common thread in these publications is the potential for occlusal overload. The purpose of this Best Evidence Consensus Statement on implant occlusal schemes was to review the literature to determine the level of scientific evidence upon which the articles are based. MATERIALS AND METHODS: Limiting the search to Clinical trials, Randomized Controlled Trials, Systematic Reviews, Meta-analyses, the key words: dental implants, occlusion, found no citations. Expanding the search to Journal articles found 1,483 results, 20 of which pertained to the question. Doing a similar search including Journal Articles, the key words: dental implants and occlusal scheme found 47 citations, 17 of which were pertinent to the question. RESULTS: After eliminating duplicates and non-relevant articles, 15 were included in the review. Nineteen additional articles were culled by going through the reference lists in the aforementioned articles. CONCLUSIONS: There is a lack of scientific evidence regarding the occlusal scheme utilized with implant restorations that will minimize or eliminate complications. In light of this lack of scientific evidence, the style of occlusion a practitioner utilizes with tooth or mucosal supported prostheses may be used with implant-supported restorations until compelling evidence dictates otherwise.

A Technique to Record and Transfer the Distance Between the Bone Crest and the Interproximal Contact Point to the Dental Laboratory to Maintain the Interdental Papilla While Fabricating Implant Supported Restorations.

The interdental papilla plays an important role in terms of esthetics and function. Management of the interdental papilla, especially around implants can be challenging. One of the factors mentioned in the literature that affects the viability of the papilla is the distance of the interdental contact point from the crest of the bone. The following case report describes a technique to predictably achieve an interdental contact area within the proper distance from the crest of the bone to help maintain the papilla for the long term.

Prosthodontic Rehabilitation of a Patient with Hypophosphatasia Using Dental Implants: A Case Report with Seven Years Follow-Up.

Hypophosphatasia is a rare metabolic inherited dento-osseous disorder. Although there is some available literature on various dental characteristics of hypophosphatasia patients, few reports focus on the effects of hypophosphatasia on the permanent dentition and prosthodontic rehabilitation, particularly in relation to the use of dental implants. This paper reports a case with hypophosphatasia and prosthodontic rehabilitation using dental implants with 7-year follow-up.

Renal Trajectory Patterns Are Associated With Postdischarge Mortality in Patients With Cirrhosis and Acute Kidney Injury.

BACKGROUND & AIMS: Little is known about long-term outcomes of acute kidney injury (AKI) in patients with cirrhosis. Outcomes can vary with stage of AKI, chronic kidney disease, and trajectory of renal function. METHODS: We collected data from the Department of Veterans Affairs and identified 6917 patients with cirrhosis who developed AKI during hospitalization at any of its 127 hospitals, from 2004 through 2014. We used latent class analysis of serial creatinine measurements during the index hospitalization to determine trajectories of renal function. RESULTS: Overall, 32% of patients died within 90 days of discharge from the hospital and 48% of patients died within 1 year. We identified 5 distinct in-hospital renal trajectories: mild AKI with full improvement (24.8% of patients died 90 within days), severe AKI with rapid improvement (24.7% of patients died within 90 days), moderate AKI with partial improvement (33.7% of patients died within 90 days), moderate to severe AKI with partial improvement (42.0% of patients died within 90 days), and severe AKI with minimal improvement (48.0% of patients died within 90 days). Trajectories were associated significantly with mortality within 90 days and 1 year of mortality. Patients with severe AKI with minimal improvement had the highest risk of death within 90 days (adjusted odds ratio, 3.08; 95% CI, 2.54-3.72) and within 1 year (adjusted odds ratio, 2.71; 95% CI, 2.25-3.27) compared with patients with mild AKI with full improvement. The highest 90-day postdischarge mortality (65.2%) was observed in patients with normal or near-normal prehospitalization renal function who developed severe AKI with minimal improvement during hospitalization. CONCLUSIONS: In an analysis of almost 7000 veterans with cirrhosis who were hospitalized for AKI, we found the pattern of renal trajectory to be associated with mortality after discharge. Renal trajectory patterns can be used to identify subgroups of patients with cirrhosis and AKI who should receive intensive postdischarge management.

Digital Custom Impression Technique to Record Emergence Profile and Fabrication of an Esthetic Implant Supported Restoration.

One of the challenges in esthetic implant supported restorations is to replicate the emergence profile of soft tissue contours created by provisional restorations. Various analog techniques have been used to achieve the most esthetic and natural emergence profile in final restorations. The evolution of digital dentistry has made dentistry easier and efficient albeit with a learning curve. The technique described here uses digital technology to describe a complete digital workflow from the provisional stage to the final restoration.

Mycoplasma pneumoniae Among Children Hospitalized With Community-acquired Pneumonia.

Background: The epidemiology of Mycoplasma pneumoniae (Mp) among US children (<18 years) hospitalized with community-acquired pneumonia (CAP) is poorly understood. Methods: In the Etiology of Pneumonia in the Community study, we prospectively enrolled 2254 children hospitalized with radiographically confirmed pneumonia from January 2010-June 2012 and tested nasopharyngeal/oropharyngeal swabs for Mp using real-time polymerase chain reaction (PCR). Clinical and epidemiological features of Mp PCR-positive and -negative children were compared using logistic regression. Macrolide susceptibility was assessed by genotyping isolates. Results: One hundred and eighty two (8%) children were Mp PCR-positive (median age, 7 years); 12% required intensive care and 26% had pleural effusion. No in-hospital deaths occurred. Macrolide resistance was found in 4% (6/169) isolates. Of 178 (98%) Mp PCR-positive children tested for copathogens, 50 (28%) had ≥1 copathogen detected. Variables significantly associated with higher odds of Mp detection included age (10-17 years: adjusted odds ratio [aOR], 10.7 [95% confidence interval {CI}, 5.4-21.1] and 5-9 years: aOR, 6.4 [95% CI, 3.4-12.1] vs 2-4 years), outpatient antibiotics ≤5 days preadmission (aOR, 2.3 [95% CI, 1.5-3.5]), and copathogen detection (aOR, 2.1 [95% CI, 1.3-3.3]). Clinical characteristics were non-specific. Conclusions: Usually considered as a mild respiratory infection, Mp was the most commonly detected bacteria among children aged ≥5 years hospitalized with CAP, one-quarter of whom had codetections. Although associated with clinically nonspecific symptoms, there was a need for intensive care in some cases. Mycoplasma pneumoniae should be included in the differential diagnosis for school-aged children hospitalized with CAP.

Increasing Health Care Burden of Chronic Liver Disease Compared With Other Chronic Diseases, 2004-2013.

BACKGROUND & AIMS: Chronic liver disease (CLD) is a common and expensive condition, and studies of CLD-related hospitalizations have underestimated the true burden of disease. We analyzed data from a large, diverse health care system to compare time trends in CLD-related hospitalizations with those in congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD). METHODS: We collected data from a large health care system in Texas on hospitalizations related to CLD (n = 27,783), CHF (n = 60,415), and COPD (n = 34,199) from January 1, 2004 through December 31, 2013. We calculated annual hospitalization rates (per 100,000) and compared hospital course, inpatient mortality, ancillary services, and readmissions. RESULTS: Compared with patients with CHF (median age, 71 years) or COPD (median age, 69 years), patients with CLD were significantly younger (median age, 57 years) (P < .01 vs CHF and COPD). Higher proportions of patients with CLD were uninsured (11.7% vs 5.4% for CHF and 5.4% for COPD, P < .01) and Hispanic (17% for CLD vs 9.3% for CHF and 5.0% for COPD, P < .01). A lower proportion of patients with CLD had Medicare (41.5% vs 68.6% with CHF and 70.1% with COPD, P < .01). From 2004 through 2013, the rate of CLD-related hospitalization increased by 92% (from 1295/100,000 to 2490/100,000), compared with 6.7% for CHF (from 3843/100,000 to 4103/100,000) and 48.8% for COPD (from 1775/100,000 to 2642/100,000). During this time period, CLD-related hospitalizations covered by Medicare increased from 31.8% to 41.5%, whereas hospitalizations covered by Medicare did not change for CHF (remained at 70%) or COPD (remained at 70%). Patients with CLD had longer hospital stays (7.3 days vs 6.2 days for CHF and 5.9 days for COPD, P < .01). A higher proportion of patients with CLD died or were discharged to hospice (14.2% vs 11.5% of patients with CHF and 9.3% of patients with COPD, P < .01), and a smaller proportion had access to postacute care (13.2% vs 23.2% of patients with CHF and 27.4% of patients with COPD, P < .01). A higher proportion of patients with CLD were readmitted to the hospital within 30 days (25% vs 21.9% of patients with CHF and 20.6% with COPD, P < .01). CONCLUSIONS: Patients with CLD, compared with selected other chronic diseases, had increasing rates of hospitalization, longer hospital stays, more readmissions, and, despite these adverse outcomes, less access to postacute care. Disease management models for CLD are greatly needed to manage the anticipated increase in hospitalizations for CLD.