Effects of glucagon-like peptide-1 receptor agonists on upper endoscopy in diabetic and nondiabetic patients.

BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) promote weight loss by suppressing appetite, enhancing satiety, regulating glucose metabolism, and delaying gastric motility. We sought to determine whether GLP-1 RA use could affect medical procedures such as EGD. METHODS: We conducted a retrospective study of 35,183 patients who underwent EGD between 2019 and 2023, 922 of whom were using a GLP-1 RAs. Data were collected regarding demographics, diabetes status, retained gastric contents during EGD, incidence of aborted EGD, and necessity for repeat EGD. RESULTS: GLP-1 RA use was associated with a 4-fold increase in the retention of gastric contents (P < .0001), 4-fold higher rates of aborted EGD (P < .0001), and twice the likelihood of requiring repeat EGD (P = .0001), even after stratifying for the presence of diabetes. CONCLUSIONS: GLP-1 RA use can lead to delayed gastric emptying, affecting EGD adequacy regardless of the presence of diabetes, and may warrant dose adjustment to improve the safety and efficacy of these procedures.

Home environment factors associated with child BMI changes during COVID-19 pandemic.

BACKGROUND: The influence of home obesogenic environments, as assessed by the validated Family Nutrition and Physical Activity (FNPA) tool, and child obesity during the COVID pandemic were evaluated using electronic health records in this retrospective cohort study. METHODS: Historical data on BMI and the FNPA screening tool were obtained from annual well-child visits within the Geisinger Health System. The study examined youth ages 2-17 that had a BMI record and an FNPA assessment prior to the pandemic (BMI 3/1/19-2/29/20), 1 BMI record 3 months into the pandemic (6/1/20-12/31/20) and 1 BMI in the second year of the pandemic (1/1/21-12/31/21). Tertiles of obesity risk by FNPA score were examined. Mixed-effects linear regression was used to examine change in BMI slope (kg/m2 per month) pre-pandemic to pandemic using FNPA summary and subscales scores as predictors and adjusting for confounding factors. RESULTS: The analyses included 6,746 children (males: 51.7%, non-Hispanic white: 86.6%, overweight:14.8%, obesity:10.3%, severe obesity: 3.9%; mean(SD) age: 5.7(2.8) years). The rate of BMI change in BMI was greatest from early pandemic compared to pre-pandemic for children in lowest versus highest tertiles of FNPA summary score (0.079 vs. 0.044 kg/m2), FNPA-Eating (0.068 vs. 0.049 kg/m2), and FNPA-Activity (0.078 vs. 0.052 kg/m2). FNPA summary score was significantly associated with change in BMI from the pre-pandemic to early pandemic period (p = 0.014), but not associated with change in BMI during the later pandemic period. CONCLUSIONS: This study provides additional insight into the changes in the rate of BMI change observed among children and adolescents in the United States during the COVID-19 pandemic. The FNPA provides ample opportunity to continue our exploration of the negative impact of the COVID-19 pandemic on the longitudinal growth patterns among children and adolescents.

Valence-state mixing and reduced magnetic moment inFe3-δGeTe2single crystals with varying Fe content probed by x-ray spectroscopy.

We present a spectroscopic study of the magnetic properties ofFe3-δGeTe2single crystals with varying Fe content, achieved by tuning the stoichiometry of the crystals. We carried out x-ray absorption spectroscopy and analyzed the x-ray circular magnetic dichroism spectra using the sum rules, to determine the orbital and spin magnetic moments of the materials. We find a clear reduction of the spin and orbital magnetic moment with increasing Fe deficiency. Magnetic susceptibility measurements show that the reduction in magnetization is accompanied by a reduced Curie temperature. Multiplet calculations reveal that the Fe2+state increasingly mixes with a higher valence state when the Fe deficiency is increased. This effect is correlated with the weakening of the magnetic moment. As single crystals are the base material for exfoliation processes, our results are relevant for the assembly of 2D magnetic heterostructures.

Extensive sex differences at the initiation of genetic recombination.

Meiotic recombination differs between males and females; however, when and how these differences are established is unknown. Here we identify extensive sex differences at the initiation of recombination by mapping hotspots of meiotic DNA double-strand breaks in male and female mice. Contrary to past findings in humans, few hotspots are used uniquely in either sex. Instead, grossly different recombination landscapes result from up to fifteen-fold differences in hotspot usage between males and females. Indeed, most recombination occurs at sex-biased hotspots. Sex-biased hotspots seem to be partly determined by chromosome structure, and DNA methylation, which is absent in females at the onset of meiosis, has a substantial role. Sex differences are also evident later in meiosis as the rate at which meiotic breaks are repaired as crossovers differs between males and females in distal regions. The suppression of distal crossovers may help to minimize age-related aneuploidy that arises owing to cohesion loss during dictyate arrest in females.

Preoperative Depression Status and 5 Year Metabolic and Bariatric Surgery Outcomes in the PCORnet Bariatric Study Cohort.

OBJECTIVE: To examine whether depression status before metabolic and bariatric surgery (MBS) influenced 5-year weight loss, diabetes, and safety/utilization outcomes in the PCORnet Bariatric Study. SUMMARY OF BACKGROUND DATA: Research on the impact of depression on MBS outcomes is inconsistent with few large, long-term studies. METHODS: Data were extracted from 23 health systems on 36,871 patients who underwent sleeve gastrectomy (SG; n=16,158) or gastric bypass (RYGB; n=20,713) from 2005-2015. Patients with and without a depression diagnosis in the year before MBS were evaluated for % total weight loss (%TWL), diabetes outcomes, and postsurgical safety/utilization (reoperations, revisions, endoscopy, hospitalizations, mortality) at 1, 3, and 5 years after MBS. RESULTS: 27.1% of SG and 33.0% of RYGB patients had preoperative depression, and they had more medical and psychiatric comorbidities than those without depression. At 5 years of follow-up, those with depression, versus those without depression, had slightly less %TWL after RYGB, but not after SG (between group difference = 0.42%TWL, P = 0.04). However, patients with depression had slightly larger HbA1c improvements after RYGB but not after SG (between group difference = - 0.19, P = 0.04). Baseline depression did not moderate diabetes remission or relapse, reoperations, revision, or mortality across operations; however, baseline depression did moderate the risk of endoscopy and repeat hospitalization across RYGB versus SG. CONCLUSIONS: Patients with depression undergoing RYGB and SG had similar weight loss, diabetes, and safety/utilization outcomes to those without depression. The effects of depression were clinically small compared to the choice of operation.

A novel cell line panel reveals non-genetic mediators of platinum resistance and phenotypic diversity in high grade serous ovarian cancer.

OBJECTIVES: Resistance to cancer therapy is an enduring challenge and accurate and reliable preclinical models are lacking. We interrogated this unmet need using high grade serous ovarian cancer (HGSC) as a disease model. METHODS: We created five in vitro and two in vivo platinum-resistant HGSC models and characterised the entire cell panel via whole genome sequencing, RNASeq and creation of intraperitoneal models. RESULTS: Mutational signature analysis indicated that platinum-resistant cell lines evolved from a pre-existing ancestral clone but a unifying mutational cause for drug resistance was not identified. However, cisplatin-resistant and carboplatin-resistant cells evolved recurrent changes in gene expression that significantly overlapped with independent samples obtained from multiple patients with relapsed HGSC. Gene Ontology Biological Pathways (GOBP) related to the tumour microenvironment, particularly the extracellular matrix, were repeatedly enriched in cisplatin-resistant cells, carboplatin-resistant cells and also in human resistant/refractory samples. The majority of significantly over-represented GOBP however, evolved uniquely in either cisplatin- or carboplatin-resistant cell lines resulting in diverse intraperitoneal behaviours that reflect different clinical manifestations of relapsed human HGSC. CONCLUSIONS: Our clinically relevant and usable models reveal a key role for non-genetic factors in the evolution of chemotherapy resistance. Biological pathways relevant to the extracellular matrix were repeatedly expressed by resistant cancer cells in multiple settings. This suggests that recurrent gene expression changes provide a fitness advantage during platinum therapy and also that cancer cell-intrinsic mechanisms influence the tumour microenvironment during the evolution of drug resistance. Candidate genes and pathways identified here could reveal therapeutic opportunities in platinum-resistant HGSC.

The Role of Urban Environments in Promoting Active and Healthy Aging: A Systematic Scoping Review of Citizen Science Approaches.

Promoting active and healthy aging in urban spaces requires environments with diverse, age-friendly characteristics. This scoping review investigated the associations between urban characteristics and active and healthy aging as identified by citizen science (CS) and other participatory approaches. Using a systematic scoping review procedure, 23 articles employing a CS or participatory approach (participant age range: 54-98 years) were reviewed. An inductive and deductive thematic analysis was completed to (a) identify local urban barriers and facilitators and (b) map them against the World Health Organization (WHO) Checklist of Essential Features of Age-Friendly Cities. A new Citizen Science Appraisal Tool (CSAT) was developed to evaluate the quality of CS and other participatory approaches included in the reviewed articles. A range of interconnected urban barriers and facilitators was generated by residents across the personal (e.g. perceived safety), environmental (e.g. unmaintained infrastructure), socio-cultural (e.g. cross-cultural activities), economic (e.g. affordable housing) and political (e.g. governmental support to migrant communities) domains. Mapping the barriers and facilitators to the WHO age-friendly checklist underscored the checklist's relevance and elucidated the need to explore barriers for migrant and cross-cultural communities and neighborhood development and alterations. The CSAT demonstrated strengths related to active engagement of residents and study outcomes leading to real-world implications. To advance the potential of CS to enrich our understanding of age-friendly environments, employing co-production to enhance relevance and sustainability of outcomes is an important strategy. Overall, employing CS highlighted the value of systematically capturing the experiences of older adults within studies aimed at promoting active and healthy aging.

A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease.

BACKGROUND: Elucidation of the genetic factors underlying chronic liver disease may reveal new therapeutic targets. METHODS: We used exome sequence data and electronic health records from 46,544 participants in the DiscovEHR human genetics study to identify genetic variants associated with serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Variants that were replicated in three additional cohorts (12,527 persons) were evaluated for association with clinical diagnoses of chronic liver disease in DiscovEHR study participants and two independent cohorts (total of 37,173 persons) and with histopathological severity of liver disease in 2391 human liver samples. RESULTS: A splice variant (rs72613567:TA) in HSD17B13, encoding the hepatic lipid droplet protein hydroxysteroid 17-beta dehydrogenase 13, was associated with reduced levels of ALT (P=4.2×10-12) and AST (P=6.2×10-10). Among DiscovEHR study participants, this variant was associated with a reduced risk of alcoholic liver disease (by 42% [95% confidence interval {CI}, 20 to 58] among heterozygotes and by 53% [95% CI, 3 to 77] among homozygotes), nonalcoholic liver disease (by 17% [95% CI, 8 to 25] among heterozygotes and by 30% [95% CI, 13 to 43] among homozygotes), alcoholic cirrhosis (by 42% [95% CI, 14 to 61] among heterozygotes and by 73% [95% CI, 15 to 91] among homozygotes), and nonalcoholic cirrhosis (by 26% [95% CI, 7 to 40] among heterozygotes and by 49% [95% CI, 15 to 69] among homozygotes). Associations were confirmed in two independent cohorts. The rs72613567:TA variant was associated with a reduced risk of nonalcoholic steatohepatitis, but not steatosis, in human liver samples. The rs72613567:TA variant mitigated liver injury associated with the risk-increasing PNPLA3 p.I148M allele and resulted in an unstable and truncated protein with reduced enzymatic activity. CONCLUSIONS: A loss-of-function variant in HSD17B13 was associated with a reduced risk of chronic liver disease and of progression from steatosis to steatohepatitis. (Funded by Regeneron Pharmaceuticals and others.).

A retrospective case control study identifies peripheral blood mononuclear cell albumin RNA expression as a biomarker for non-alcoholic fatty liver disease.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) improves after bariatric surgery. The aim of this study was to determine whether peripheral blood mononuclear cell albumin gene expression was related to NAFLD and whether albumin (ALB) and alpha fetoprotein (AFP) expression could be detected in whole blood and visceral adipose tissue. METHODS: Using a retrospective case control study design, RNA isolated from peripheral blood mononuclear cells from patients prior to undergoing bariatric surgery was used for pooled microarray analysis. Quantitative polymerase chain reaction (QPCR) was used to analyze whole blood and visceral adipose tissue. Liver histology was obtained via intra-operative biopsy and clinical data extracted from the electronic health record. RESULTS: The albumin (ALB) gene was the second most up-regulated found in microarray analysis of peripheral blood mononuclear cell RNA from patients with hepatic lobular inflammation versus normal liver histology. Transcript levels of ALB were significantly different across those with normal (n = 50), steatosis (n = 50), lobular inflammation (n = 50), and peri-sinusoidal fibrosis (n = 50) liver histologies, with lobular inflammation 3.9 times higher than those with normal histology (p < 0.017). Albumin expression levels decreased in 11/13 patients in paired samples obtained prior to and at 1 year after Roux-en-Y gastric bypass surgery. ALB expression could be detected in 23 visceral adipose tissue samples obtained intra-operatively and in 18/19 available paired whole blood samples. No significant correlation was found between ALB expression in visceral adipose tissue and whole blood RNA samples. Alpha fetoprotein expression as a marker of early hepatocytic differentiation was detected in 17/17 available VAT RNA samples, but in only 2/17 whole blood RNA samples. CONCLUSION: Albumin RNA expression from blood cells may serve as a biomarker of NAFLD. Albumin and alpha fetoprotein appear to be ubiquitously expressed in visceral adipose tissue in patients with extreme obesity.

Tigecycline to treat Stenotrophomonas maltophilia ventilator-associated pneumonia in a trauma intensive care unit as a result of a drug shortage: A case series.

WHAT IS KNOWN AND OBJECTIVE: Stenotrophomonas maltophilia is an intrinsically multidrug-resistant (MDR) organism which commonly presents as a respiratory tract infection. S. maltophilia is typically treated with high-dose sulfamethoxazole/trimethoprim (SMX/TMP). However, SMX/TMP and other treatment options for S. maltophilia can be limited because of resistance, allergy, adverse events or unavailability of the drug; use of novel agents may be necessary to adequately treat this MDR infection and overcome these limitations. CASE DESCRIPTION: This small case series describes two patients who underwent treatment with tigecycline for ventilator-associated pneumonia (VAP) caused by S. maltophilia after admission to a trauma intensive care unit. At the time of admission for the two reported patients, a national drug shortage of intravenous (IV) SMX/TMP prevented its use. Tigecycline was chosen as a novel agent to treat S. maltophilia VAP based on culture and susceptibility data, and it was used successfully. Both patients showed clinical signs of improvement with eventual cure and discharge from the hospital after treatment with tigecycline, and one patient demonstrated confirmed microbiological cure with a negative repeat bronchoscopic bronchoalveolar lavage (BAL). WHAT IS NEW AND CONCLUSION: To our knowledge, this small case series is the first documentation of utilizing tigecycline to treat S. maltophilia VAP in the United States. Although it likely should not be considered as a first-line agent, tigecycline proved to be an effective treatment option in the two cases described in the setting of a national drug shortage of the drug of choice.

Visual attention, EEG alpha power and T7-Fz connectivity are implicated in prosthetic hand control and can be optimized through gaze training.

BACKGROUND: Prosthetic hands impose a high cognitive burden on the user that often results in fatigue, frustration and prosthesis rejection. However, efforts to directly measure this burden are sparse and little is known about the mechanisms behind it. There is also a lack of evidence-based training interventions designed to improve prosthesis hand control and reduce the mental effort required to use them. In two experiments, we provide the first direct evaluation of this cognitive burden using measurements of EEG and eye-tracking (Experiment 1), and then explore how a novel visuomotor intervention (gaze training; GT) might alleviate it (Experiment 2). METHODS: In Experiment 1, able-bodied participants (n = 20) lifted and moved a jar, first using their anatomical hand and then using a myoelectric prosthetic hand simulator. In experiment 2, a GT group (n = 12) and a movement training (MT) group (n = 12) trained with the prosthetic hand simulator over three one hour sessions in a picking up coins task, before returning for retention, delayed retention and transfer tests. The GT group received instruction regarding how to use their eyes effectively, while the MT group received movement-related instruction typical in rehabilitation. RESULTS: Experiment 1 revealed that when using the prosthetic hand, participants performed worse, exhibited spatial and temporal disruptions to visual attention, and exhibited a global decrease in EEG alpha power (8-12 Hz), suggesting increased cognitive effort. Experiment 2 showed that GT was the more effective method for expediting prosthesis learning, optimising visual attention, and lowering conscious control - as indexed by reduced T7-Fz connectivity. Whilst the MT group improved performance, they did not reduce hand-focused visual attention and showed increased conscious movement control. The superior benefits of GT transferred to a more complex tea-making task. CONCLUSIONS: These experiments quantify the visual and cortical mechanisms relating to the cognitive burden experienced during prosthetic hand control. They also evidence the efficacy of a GT intervention that alleviated this burden and promoted better learning and transfer, compared to typical rehabilitation instructions. These findings have theoretical and practical implications for prosthesis rehabilitation, the development of emerging prosthesis technologies and for the general understanding of human-tool interactions.

CCL20 is up-regulated in non-alcoholic fatty liver disease fibrosis and is produced by hepatic stellate cells in response to fatty acid loading.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent complication of extreme obesity. Loading of the liver with fat can progress to inflammation and fibrosis including cirrhosis. The molecular factors involved in the progression from simple steatosis to fibrosis remain poorly understood. METHODS: Gene expression profiling using microarray, PCR array, and RNA sequencing was performed on RNA from liver biopsy tissue from patients with extreme obesity. Patients were grouped based on histological findings including normal liver histology with no steatosis, lobular inflammation, or fibrosis, and grades 1, 2, 3, and 4 fibrosis with coexistent steatosis and lobular inflammation. Validation of expression was conducted using quantitative PCR. Serum analysis was performed using ELISA. Expression analysis of hepatocytes and hepatic stellate cells in response to lipid loading were conducted in vitro using quantitative PCR and ELISA. RESULTS: Three orthogonal methods to profile human liver biopsy RNA each identified the chemokine CCL20 (CC chemokine ligand 20 or MIP-3 alpha) gene as one of the most up-regulated transcripts in NAFLD fibrosis relative to normal histology, validated in a replication group. CCL20 protein levels in serum measured in 224 NAFLD patients were increased in severe fibrosis (p < 0.001), with moderate correlation of hepatic transcript levels and serum levels. Expression of CCL20, but not its cognate receptor CC chemokine receptor 6, was significantly (p < 0.001) increased in response to fatty acid loading in LX-2 hepatic stellate cells, with relative increases greater than those in HepG2 hepatocyte cells. CONCLUSIONS: These results suggest that expression of CCL20, an important inflammatory mediator, is increased in NAFLD fibrosis. CCL20 serves as a chemoattractant molecule for immature dendritic cells, which have been shown to produce many of the inflammatory molecules that mediate liver fibrosis. These data also point to hepatic stellate cells as a key cell type that may respond to lipid loading of the liver.

TM6SF2 rs58542926 impacts lipid processing in liver and small intestine.

The transmembrane 6 superfamily member 2 (TM6SF2) loss-of-function variant rs58542926 is a genetic risk factor for nonalcoholic fatty liver disease and progression to fibrosis but is paradoxically associated with lower levels of hepatically derived triglyceride-rich lipoproteins. TM6SF2 is expressed predominantly in liver and small intestine, sites for triglyceride-rich lipoprotein biogenesis and export. In light of this, we hypothesized that TM6SF2 may exhibit analogous effects on both liver and intestine lipid homeostasis. To test this, we genotyped rs58542926 in 983 bariatric surgery patients from the Geisinger Medical Center for Nutrition and Weight Management, Geisinger Health System, in Pennsylvania and from 3,556 study participants enrolled in the Amish Complex Disease Research Program. Although these two cohorts have different metabolic profiles, carriers in both cohorts had improved fasting lipid profiles. Importantly, following a high-fat challenge, carriers in the Amish Complex Disease Research Program cohort exhibited significantly lower postprandial serum triglycerides, suggestive of a role for TM6SF2 in the small intestine. To gain further insight into this putative role, effects of TM6SF2 deficiency were studied in a zebrafish model and in cultured human Caco-2 enterocytes. In both systems TM6SF2 deficiency resulted in defects in small intestine metabolism in response to dietary lipids, including significantly increased lipid accumulation, decreased lipid clearance, and increased endoplasmic reticulum stress. CONCLUSIONS: These data strongly support a role of TM6SF2 in the regulation of postprandial lipemia, potentially through a similar function for TM6SF2 in the lipidation and/or export of both hepatically and intestinally derived triglyceride-rich lipoproteins. (Hepatology 2017;65:1526-1542).

Treatment of Achromobacter Ventilator-Associated Pneumonia in Critically Ill Trauma Patients.

BACKGROUND: Achromobacter sp are nonfermenting Gram-negative bacilli (NFGNB) that rarely cause severe infections, including ventilator-associated pneumonia (VAP). Data on the treatment of Achromobacter pneumonia are very limited, and the organism has been associated with a high mortality rate. Thus, more data are needed on treating this organism. OBJECTIVE: To evaluate the treatment of Achromobacter VAP in critically ill trauma patients. METHODS: This retrospective, observational study evaluated critically ill trauma patients who developed Achromobacter VAP. A previously published pathway for the diagnosis and management of VAP was used according to routine patient care. This included the use of quantitative bronchoscopic bronchoalveolar lavage cultures to definitively diagnose VAP. RESULTS: A total of 37 episodes of Achromobacter VAP occurred in 34 trauma intensive care unit patients over a 15-year period. The most commonly used definitive antibiotics were imipenem/cilastatin, cefepime, or trimethoprim/sulfamethoxazole. The primary outcome of clinical success was achieved in 32 of 37 episodes (87%). This is similar to previous studies of other NFGNB VAP (eg, Pseudomonas, Acinetobacter) from the study center. Microbiological success was seen in 21 of 28 episodes (75%), and VAP-related mortality was 9% (3 of 34 patients). CONCLUSIONS: Achromobacter is a rare but potentially serious cause of VAP in critically ill patients. In this study, there was an acceptable success rate compared with other causes of NFGNB VAP in this patient population.

Changes in telomere length 3-5 years after gastric bypass surgery.

Increased inflammation and oxidative stress associated with obesity can accelerate aging. Telomere length (TL) has the capacity to serve as an aging indicator at the cellular level. Obesity has a known association with shorter TL. This study evaluated TL of immune cells in a population of obese individuals who underwent gastric bypass surgery. Pre- and post-operative DNA samples were available for 50 subjects who had gastric bypass surgery. DNA was analyzed via quantitative polymerase chain reaction to determine TL. Changes in TL were evaluated by comparing TL at baseline to TL at 3-5 years post gastric bypass surgery. Sixty percent of the individuals in the study observed an increase in TL. Significant lengthening was observed for those with the shortest baseline TL (P=0.0011), but not for those with intermediate baseline TL (P=0.411) or longest baseline TL (P=0.207). Change in TL was negatively correlated with age and triglycerides but not correlated with weight loss induced by bariatric surgery. This study confirms that TL lengthening is observed post bariatric surgery and is the first to detect TL lengthening 3-5 years after surgery.

An Update on Aerosolized Antibiotics for Treating Hospital-Acquired and Ventilator-Associated Pneumonia in Adults.

OBJECTIVE: A significant percentage of patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) have poor outcomes with intravenous antibiotics. It is not clear if adding aerosolized antibiotics improves treatment. This review is an update on using aerosolized antibiotics for treating HAP/VAP in adults. DATA SOURCES: PubMed search using the terms "aerosolized antibiotics pneumonia," "nebulized antibiotics pneumonia," and "inhaled antibiotics pneumonia." Reference lists from identified articles were also searched. STUDY SELECTION AND DATA EXTRACTION: Clinical studies of aerosolized antibiotics for treating HAP/VAP in adults from July 2010 to March 2017. This article updates a previous review on this topic written in mid-2010. DATA SYNTHESIS: The size and quality of studies have improved dramatically in the recent time period compared to previous studies. However, there still are not large randomized controlled trials available. Colistin and aminoglycosides were the most commonly studied agents, and the most common pathogens were Pseudomonas and Acinetobacter. The clinical efficacy of adding aerosolized antibiotics was mixed. Approximately half of the studies showed better outcomes, and none showed worse outcomes. Aerosolized antibiotics appear to be relatively safe, though pulmonary adverse events can occur. Attention to proper administration technique in mechanically ventilated patients is required, including the use of vibrating plate nebulizers. CONCLUSIONS: Adding aerosolized antibiotics to intravenous antibiotics may improve the outcomes of adult patients with HAP/VAP in some settings. It seems reasonable to add aerosolized antibiotics in patients with multidrug-resistant organisms or who appear to be failing therapy. Clinicians should pay attention to potential adverse events and proper administration technique.

Optics research at the U.S. Army Research Laboratory.

The U.S. Army Research Laboratory (ARL) is the Army's premier laboratory for land forces. The Army relies on ARL for scientific discoveries, technological advances, and analyses that enable capabilities a future Army will need to persevere over adversaries. Although a relatively young organization that will celebrate 25 years of the discovery, innovation, and transition of science and technology in October 2017, ARL has already had significant impact in a wide range of scientific and technological disciplines. In this paper, we highlight some of its past and recent achievements in optics and photonics.

Successful sperm extraction and live birth after radiation, androgen deprivation and surgical castration for treatment of metastatic prostate cancer.

Fertility preservation has become an important aspect of cancer treatment given the gonadotoxic effects of oncologic therapies. It is now considered standard of care to offer sperm banking to men undergoing treatment for primaries that affect young individuals. Less is known regarding fertility preservation of patients afflicted with prostate cancer. This cohort has progressively expanded and grown younger in the post-PSA era. Prostatectomy, radiation, chemotherapy and androgen blockade all pose unique challenges to the infertility specialist. Optimum management becomes even more uncertain for those men with metastatic prostate cancer. Most of these individuals will have received multiple forms of therapy, each carrying a distinct insult to the patient's reproductive potential. We describe a case of successful ex vivo sperm extraction and live birth in a patient previously treated with radiation and chronic androgen deprivation for metastatic prostate cancer. The presented case demonstrates that conception after radiation therapy and chronic androgen deprivation is feasible. We propose that fertility counselling and sperm cryopreservation should be considered for all prostate cancer patients. Additionally, for those individuals undergoing external beam radiotherapy, testicular shielding should be routinely offered in the event further family building is desired.

Bariatric surgery is associated with improvement in kidney outcomes.

Severe obesity is associated with increased risk of kidney disease. Whether bariatric surgery reduces the risk of adverse kidney outcomes is uncertain. To resolve this we compared the risk of estimated glomerular filtration rate (eGFR) decline of ≥30% and doubling of serum creatinine or end-stage renal disease (ESRD) in 985 patients who underwent bariatric surgery with 985 patients who did not undergo such surgery. Patients were matched on demographics, baseline body mass index, eGFR, comorbidities, and previous nutrition clinic use. Mean age was 45 years, 97% were white, 80% were female, and 33% had baseline eGFR <90 ml/min per 1.73 m(2). Mean 1-year weight loss was 40.4 kg in the surgery group compared with 1.4 kg in the matched cohort. Over a median follow-up of 4.4 years, 85 surgery patients had an eGFR decline of ≥30% (22 had doubling of serum creatinine/ESRD). Over a median follow-up of 3.8 years, 177 patients in the matched cohort had an eGFR decline of ≥30% (50 had doubling of serum creatinine/ESRD). In adjusted analysis, bariatric surgery patients had a significant 58% lower risk for an eGFR decline of ≥30% (hazard ratio 0.42, 95% confidence interval 0.32-0.55) and 57% lower risk of doubling of serum creatinine or ESRD (hazard ratio 0.43, 95% confidence interval: 0.26-0.71) compared with the matched cohort. Results were generally consistent among subgroups of patients with and without eGFR <90 ml/min per 1.73 m(2), hypertension, and diabetes. Thus, bariatric surgery may be an option to prevent kidney function decline in severely obese individuals.

Prostate Specific Membrane Antigen Positron Emission Tomography May Improve the Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging in Localized Prostate Cancer.

PURPOSE: Positron emission tomography using ligands targeting prostate specific membrane antigen has recently been introduced. Positron emission tomography imaging with (68)Ga-PSMA-HBED-CC has been shown to detect metastatic prostate cancer lesions at a high rate. In this study we compare multiparametric magnetic resonance imaging and prostate specific membrane antigen positron emission tomography of the prostate with whole mount ex vivo prostate histopathology to determine the true sensitivity and specificity of these imaging modalities for detecting and locating tumor foci within the prostate. MATERIALS AND METHODS: In a prospective clinical trial setting 20 patients with localized prostate cancer and a planned radical prostatectomy were recruited. All patients underwent multiparametric magnetic resonance imaging and positron emission tomography before surgery, and whole mount histopathology slides were directly compared to the images. European Society of Urogenital Radiology guidelines for reporting magnetic resonance imaging were used as a template for regional units of analysis. The uropathologist and radiologists were blinded to individual components of the study, and the final correlation was performed by visual and deformable registration analysis. RESULTS: A total of 50 clinically significant lesions were identified from the whole mount histopathological analysis. Based on regional analysis the sensitivity, specificity, positive predictive value and negative predictive value for multiparametric magnetic resonance imaging were 44%, 94%, 81% and 76%, respectively. With prostate specific membrane antigen positron emission tomography the sensitivity, specificity, positive predictive value and negative predictive value were 49%, 95%, 85% and 88%, respectively. Prostate specific membrane antigen positron emission tomography yielded a higher specificity and positive predictive value. CONCLUSIONS: A significant proportion of cancers are potentially missed and underestimated by both imaging modalities. Prostate specific membrane antigen positron emission tomography may be used in addition to multiparametric magnetic resonance imaging to help improve local staging in those patients undergoing retropubic radical prostatectomy.