The role of adjuvant pharmacotherapy with liraglutide for patients with inadequate weight loss following bariatric surgery.

PURPOSE: Despite the benefits of bariatric surgery for many patients, there are a proportion of patients who do not achieve adequate weight loss. We evaluate the role of liraglutide as adjuvant pharmacotherapy in those who respond poorly to weight loss surgery. MATERIALS AND METHODS: A non-controlled, prospective, open-label cohort study in which participants are prescribed liraglutide following inadequate response to weight loss surgery. The efficacy and tolerability of liraglutide was measured through measurement of BMI and monitoring of side effect profile. RESULTS: A total of 68 partial responders to bariatric surgery were included in the study, 2 participants were lost to follow-up. Overall 89.7% lost weight on liraglutide, with 22.1% showing a good response (>10% total body weight loss). There were 41 patients who discontinued liraglutide mainly due to cost. CONCLUSION: Liraglutide is efficacious in achieving weight loss and reasonably well tolerated in patients who have inadequate weight loss post-bariatric surgery.

Primary CNS lymphoma: update on molecular pathogenesis and therapy.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of extra-nodal non-Hodgkin lymphoma that as a brain tumor poses a unique set of challenges in diagnosis and management. With the advent of next-generation sequencing, we review updates in the understanding of its molecular and genomic pathogenesis. We also highlight key issues in management, with a focus on emerging technologies and new biological therapies including monoclonal antibodies, IMiDs, BTK inhibitors, PD-1 inhibitors, and CAR-T therapy. Integration of these approaches will likely enhance induction and consolidation strategies to suppress NF-κB activation and the anti-tumor immune response, while minimizing the often noxious effects of genotoxic approaches.

Fertility, pregnancy and post partum management after bariatric surgery: a narrative review.

•Of the women who gave birth in Australia in 2018, 47% had overweight or obesity, with obesity being associated with both maternal and fetal complications. •Bariatric surgery improves fertility and some pregnancy-related outcomes. •Following bariatric surgery, pregnancy should be delayed by at least 12-18 months due to adverse pregnancy outcomes associated with rapid weight loss. •Contraception should be prescribed after bariatric surgery, although the effectiveness of the oral contraceptive pill may be reduced due to malabsorption and contraceptive devices such as intrauterine devices should be considered as first line therapy. •After bariatric surgery, women should undergo close monitoring for nutritional insufficiencies before, during and after pregnancy. Expert opinion recommends these women undergo dietary assessment and supplementation to prevent micronutrient deficiencies. •Bariatric surgeons, bariatric medical practitioners, bariatric dieticians, the patient's usual general practitioner, obstetricians, and maternity specialists should be involved to assist in the multidisciplinary management of these complex patients.

Natural History of Chronic Hepatitis B Infection Among Chinese Children and Young Adults: A Single-Center Experience.

OBJECTIVES: There are limited data on the natural history of chronic hepatitis B virus (HBV) infection in Asian American children. The aim of the present study was to describe a single-center experience of chronic HBV infection in Chinese American patients in New York City. METHODS: A retrospective chart review was conducted for patients with chronic HBV infection who had pediatric visits from 2006 to 2017. Clinical and laboratory data were collected to characterize the status of HBV infection and its disease course both cross-sectionally and longitudinally. Available maternal charts were reviewed. RESULTS: Of the total 353 patients, 72 patients (20%) were US-born. Positive hepatitis B envelope antigen (HBeAg) was documented in 208 patients (58%). Three phases of chronic HBV infection were categorized for 329 patients: immune-tolerant 112 (34%), HBeAg-positive immune-active 47 (14%), and inactive carrier 82 (25%). The remaining 88 patients (27%) did not fit into a particular category with 26 of 88 patients meeting the criteria for inactive carrier except for mildly elevated alanine aminotransferase. Age and liver enzyme levels were significantly different between HBeAg-positive and HBeAg-negative groups (P < 0.05). Among 179 patients followed for ≥5 years, the spontaneous seroconversion rate was 38%. In eight patients with linked maternal data, all children completed the HBV vaccine series and seven of eight received hepatitis B immunoglobulin. All mothers were HBeAg-positive with high HBV DNA and had no anti-viral therapy during pregnancy. CONCLUSIONS: Both immune-tolerant and inactive carrier phases were common for chronic HBV infection with a spontaneous seroconversion rate of 38%. All US-born patients were born in the era of implemented universal immune-prophylaxis.

Nasal Peak Inspiratory Flow in Healthy and Obstructed Patients: Systematic Review and Meta-Analysis.

OBJECTIVES: Nasal peak inspiratory flow (NPIF) is a practical and affordable tool that measures maximum inspiratory flow rate through both nostrils. Although NPIF values for healthy controls and patients appear to differ considerably, a generally expected value for populations with and without nasal obstruction has yet to be established. The aim of this systematic review and meta-analysis was to determine the mean NPIF value in populations with and without nasal obstruction. METHODS: Medline (1946-) and Embase (1947-) were searched until July 1, 2017. A search strategy was used to identify studies that reported NPIF values for defined healthy or disease states. All studies providing original data were included. The study population was defined as having either normal nasal breathing or nasal obstruction. A meta-analysis of the mean data was presented in forest plots, and data were presented as mean (95% confidence interval [CI]). RESULTS: The search yielded 1,526 studies, of which 29 were included. The included studies involved 1,634 subjects with normal nasal breathing and 817 subjects with nasal obstruction. The mean NPIF value for populations with normal nasal breathing was 138.4 (95% CI: 127.9-148.8) L/min. The mean value for populations with nasal obstruction was 97.5 (95% CI: 86.1-108.8) L/min. CONCLUSIONS: Current evidence confirms a difference between mean NPIF values of populations with and without nasal obstruction. The mean value of subjects with no nasal obstruction is 138.4 L/min, and the mean value of nasally obstructed populations is 97.5 L/min. Prospective studies adopting a standardized procedure are required to further assess normative NPIF values. Laryngoscope, 131:260-267, 2021.

Cost-effectiveness analysis of multimodal prognostication in cardiac arrest with EEG monitoring.

OBJECTIVE: To determine cost-effectiveness parameters for EEG monitoring in cardiac arrest prognostication. METHODS: We conducted a cost-effectiveness analysis to estimate the cost per quality-adjusted life-year (QALY) gained by adding continuous EEG monitoring to standard cardiac arrest prognostication using the American Academy of Neurology Practice Parameter (AANPP) decision algorithm: neurologic examination, somatosensory evoked potentials, and neuron-specific enolase. We explored lifetime cost-effectiveness in a closed system that incorporates revenue back into the medical system (return) from payers who survive a cardiac arrest with good outcome and contribute to the health system during the remaining years of life. Good outcome was defined as a Cerebral Performance Category (CPC) score of 1-2 and poor outcome as CPC of 3-5. RESULTS: An improvement in specificity for poor outcome prediction of 4.2% would be sufficient to make continuous EEG monitoring cost-effective (baseline AANPP specificity = 83.9%). In sensitivity analysis, the effect of increased sensitivity on the cost-effectiveness of EEG depends on the utility (u) assigned to a poor outcome. For patients who regard surviving with a poor outcome (CPC 3-4) worse than death (u = -0.34), an increased sensitivity for poor outcome prediction of 13.8% would make AANPP + EEG monitoring cost-effective (baseline AANPP sensitivity = 76.3%). In the closed system, an improvement in sensitivity of 1.8% together with an improvement in specificity of 3% was sufficient to make AANPP + EEG monitoring cost-effective, assuming lifetime return of 50% (USD $70,687). CONCLUSION: Incorporating continuous EEG monitoring into cardiac arrest prognostication is cost-effective if relatively small improvements in sensitivity and specificity are achieved.

Tombusvirus p19 Captures RNase III-Cleaved Double-Stranded RNAs Formed by Overlapping Sense and Antisense Transcripts in Escherichia coli.

Antisense transcription is widespread in bacteria. By base pairing with overlapping sense RNAs, antisense RNAs (asRNA) can form double-stranded RNAs (dsRNA), which are cleaved by RNase III, a dsRNA endoribonuclease. The ectopic expression of plant Tombusvirus p19 in Escherichia coli stabilizes ∼21-nucleotide (nt) dsRNA RNase III decay intermediates, which enabled us to characterize otherwise highly unstable asRNA by deep sequencing of p19-captured dsRNA. RNase III-produced small dsRNA were formed at most bacterial genes in the bacterial genome and in a plasmid. We classified the types of asRNA in genomic clusters producing the most abundant p19-captured dsRNA and confirmed RNase III regulation of asRNA and sense RNA decay at three type I toxin-antitoxin loci and at a coding gene, rsd Furthermore, we provide potential evidence for the RNase III-dependent regulation of CspD protein by asRNA. The analysis of p19-captured dsRNA revealed an RNase III sequence preference for AU-rich sequences 3 nucleotides on either side of the cleavage sites and for GC-rich sequences in the 2-nt overhangs. Unexpectedly, GC-rich sequences were enriched in the middle section of p19-captured dsRNA, suggesting some unexpected sequence bias in p19 protein binding. Nonetheless, the ectopic expression of p19 is a sensitive method for identifying antisense transcripts and RNase III cleavage sites in dsRNA formed by overlapping sense and antisense transcripts in bacteria.

Genomics of response to immune checkpoint therapies for cancer: implications for precision medicine.

Immune checkpoint blockade (ICB) therapies, which potentiate the body's natural immune response against tumor cells, have shown immense promise in the treatment of various cancers. Currently, tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are the primary biomarkers evaluated for clinical management of cancer patients across histologies. However, the wide range of responses has demonstrated that the specific molecular and genetic characteristics of each patient's tumor and immune system must be considered to maximize treatment efficacy. Here, we review the various biological pathways and emerging biomarkers implicated in response to PD-(L)1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) therapies, including oncogenic signaling pathways, human leukocyte antigen (HLA) variability, mutation and neoantigen burden, microbiome composition, endogenous retroviruses (ERV), and deficiencies in chromatin remodeling and DNA damage repair (DDR) machinery. We also discuss several mechanisms that have been observed to confer resistance to ICB, such as loss of phosphatase and tensin homolog (PTEN), loss of major histocompatibility complex (MHC) I/II expression, and activation of the indoleamine 2,3-dioxygenase 1 (IDO1) and transforming growth factor beta (TGFß) pathways. Clinical trials testing the combination of PD-(L)1 or CTLA-4 blockade with molecular mediators of these pathways are becoming more common and may hold promise for improving treatment efficacy and response. Ultimately, some of the genes and molecular mechanisms highlighted in this review may serve as novel biological targets or therapeutic vulnerabilities to improve clinical outcomes in patients.

Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy.

The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide.

Retrospective Analysis of Patient Presentations at the Sydney (Australia) Royal Easter Show from 2012 to 2014.

Introduction Comprehensive studies on the relationship between patient demographics and subsequent treatment and disposition at a single mass-gathering event are lacking. The Sydney Royal Easter Show (SRES; Sydney Olympic Park, New South Wales, Australia) is an annual, 14-day, agricultural mass-gathering event occurring around the Easter weekend, attracting more than 800,000 patrons per year. In this study, patient records from the SRES were analyzed to examine relationships between weather, crowd size, day of week, and demographics on treatment and disposition. This information would help to predict factors affecting patient treatment and disposition to guide ongoing training of first responders and to evaluate the appropriateness of staffing skills mix at future events. Hypothesis Patient demographics, environmental factors, and attendance would influence the nature and severity of presentations at the SRES, which would influence staffing requirements. METHODS: A retrospective analysis of 4,141 patient record forms was performed for patients who presented to St John Ambulance (Australian Capital Territory, Australia) at the SRES between 2012 and 2014 inclusive. Presentation type was classified using a previously published minimum data set. Data on weather and crowd size were obtained from the Australian Bureau of Meteorology (Melbourne, Victoria, Australia) and the SRES, respectively. Statistical analyses were performed using SPSS v22 (IBM; Armonk, New York USA). RESULTS: Between 2012 to 2014, over 2.5 million people attended the SRES with 4,141 patients treated onsite. As expected, the majority of presentations were injuries (49%) and illnesses (46%). Although patient demographics and presentation types did not change over time, the duration of treatment increased. A higher proportion of patients were discharged to hospital or home compared to the proportion of patients discharged back to the event. Patients from rural/regional locations (accounting for 15% of all patients) were more likely to require advanced treatment, health professional review, and were more likely to be discharged to hospital or home rather than discharged back to the event. Extremes of temperature were associated with a lower crowd size and higher patient presentation rate (PPR), but had no impact on transfer or referral rates to hospital. CONCLUSION: This study demonstrated that analyses of patient presentations at an agricultural show provide unique insights on weather, attendance, and demographic features that correlated with treatment and disposition. These data can help guide organizers with information on how to better staff and train health care providers at future mass-gathering events of this type. Crabtree N , Mo S , Ong L , Jegathees T , Wei D , Fahey D , Liu J . Retrospective analysis of patient presentations at the Sydney (Australia) Royal Easter Show from 2012 to 2014. Prehosp Disaster Med. 2017;32(2)187-194.

Monitoring tectonic uplift and paleoenvironmental reconstruction for marine terraces near Maǧaracik and Samandaǧ, Hatay Province, Turkey.

Near Hatay, the Antakya-Samandag-Cyprus Fault (ASCF), East Anatolian and Dead Sea Fault Zones, the large faults that form the edges of the African, Anatolian, Cyprus and Arabian Plates, all produce large earthquakes, which have decimated Hatay repeatedly. Near Samandag, Hatay, differential vertical displacement on the ASCF has uplifted the southeastern side relative to northwestern side, producing large fault scarps that parallel the Asi (Orontes) River. Tectonic uplift coupled with Quaternary sealevel fluctuations has produced several stacked marine terraces stranded above current sealevel. This study dated 24 mollusc samples from 10 outcrops on six marine terraces near Samandag electron spin resonance (ESR). Ages were calculated using time-averaged and volumetrically averaged external dose rates, modelled by assuming typical water depths for the individual species and sediment thicknesses estimated from geological criteria. Uplift rates were then calculated for each fault block. At all the Magaracik terraces, the dates suggest that many shells were likely reworked. On the 30 m terrace at Magaracik IV (UTM 766588-3999880), Lithophagus burrows with in situ shells cross the unconformity. One such shell dated to 62 ± 6 ka, setting the minimum possible age for the terrace. For all the Magaracik terraces at ∼30 m above mean sealevel (amsl), the youngest ages for the reworked shells, which averaged 60 ± 3 ka for six separate analyses, sets the maximum possible age for this unit. Thus, the terrace must date to 60-62 ± 3 ka, at the MIS 3/4 boundary when temperatures and sealevels were fluctuating rapidly. Older units dating to MIS 7, 6, and 5 likely were being eroded to supply some fossils found in this terrace. At Magaracik Dump (UTM 765391-4001048), ∼103 m amsl, Ostrea and other shells were found cemented in growth position to the limestone boulders outcropping there <2.0 m above a wave-eroded notch. If the oysters grew at the same time as the wave-cut notch and the related terrace, the date, 91 ± 13 ka, for the oysters, this fault block has been uplifted at 1.19 ± 0.15 m ky(-1), since MIS 5c. At Samandag Kurt Stream at 38 m amsl, molluscs were deposited fine sandy gravel, which was likely formed in a large tidal channel. Four molluscs averaged 116 ± 5 ka. If these molluscs have not been reworked, this fault block has uplifted at 0.34 ± 0.05 m ky(-1) since the MIS 5d/5e boundary. The differences in these uplift rates suggests that at least one, and possibly two, hitherto undiscovered faults may separate the Magaracik Dump site from the other Magaracik sites and from the Samandag Kurt Stream site.