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Background: In kidney transplantation, concerns have been raised regarding increased incidence of viral opportunistic infections in hepatitis C virus (HCV) nucleic acid test (NAT)-negative (-) recipients who received HCV NAT-positive (+) donor kidneys, specifically BK polyomavirus (BKPyV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). The purpose of this study was to determine the incidence of these three viral opportunistic infections in HCV NAT- recipients who have undergone kidney transplantation with HCV NAT+ donor kidneys at our institution., Methods: This was an Institutional Review Board-approved, single-center, retrospective case-control study of HCV NAT- kidney transplant recipients with HCV NAT+ donors from 2018 to 2021. The primary outcome was the cumulative incidence of viral infections of BKPyV, CMV, and/or EBV within 1 year following kidney transplantation., Results: A total of 231 patients were included, 77 in the exposed (donor HCV NAT+) group and 154 in the control (donor HCV NAT-) group. The adjusted cumulative incidence of viremia within 1 year did not statistically differ between groups (77% exposed group versus 66% for the control group, hazard ratio 1.34, 95% confidence interval 0.95-1.89). In addition, no statistically significant differences were observed for secondary outcomes with the exception of CMV viremia (62% exposed versus 49% control, p = 0.021). However, there were more patients in the exposed group at high risk for CMV viremia based on serostatus (CMV Donor+/Recipient-, D+/R-)., Conclusion: Among patients who received HCV NAT+ donor kidneys, no clear association was observed between exposure to HCV NAT+ donor kidneys and viral infections of BKPyV, CMV, or EBV., (© 2024 Wiley Periodicals LLC.)

Spinal cord stimulation (SCS) has emerged as a novel therapeutic option for refractory complex regional pain syndrome (CRPS). However, SCS placement is often complicated by a prior history of surgical manipulation and hardware implantation along the spinal column. Through this case exploration, we aim to expand the technical approach to SCS implantation in CRPS and encourage further research into innovative approaches for this treatment modality. Our patient is a 61-year-old female with a past medical history of bilateral C7 cervical pedicle fracture status and extensive surgical manipulation, including cervical laminectomy and hardware placement along the cervical spine. The development of CRPS refractory to conventional therapies complicated her course. We obtained non-contrast computed tomography (CT) to confirm intact lamina in vertebral levels below C3 and proceeded with the SCS trial with successful lead placement up to C5. Despite prior surgical manipulation of the vertebral spine hindering our ability to access the ideal C2 level, we were able to achieve significant coverage up to the C5 level. Obtaining non-contrast CT preoperatively and carefully assessing the epidural space patency were integral to our ability to assess the feasibility of lead placement in a patient with extensive hardware. Through this approach, we are able to offer SCS to patients who would otherwise be precluded from this modality., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Zaidi et al.)

Background and Aims: Inflammatory bowel disease [IBD] is associated with high rates of post-colonoscopy colorectal cancer [PCCRC], but further in-depth qualitative analyses are required to determine whether they result from inadequate surveillance or aggressive IBD cancer evolution., Methods: All IBD patients who had a colorectal cancer [CRC] diagnosed between January 2015 and July 2019 and a recent [<4 years] surveillance colonoscopy at one of four English hospital trusts underwent root cause analyses as recommended by the World Endoscopy Organisation to identify plausible PCCRC causative factors., Results: In total, 61% [n = 22/36] of the included IBD CRCs were PCCRCs. They developed in patients with high cancer risk factors [77.8%; n = 28/36] requiring annual surveillance, yet 57.1% [n = 20/35] had inappropriately delayed surveillance. Most PCCRCs developed in situations where [i] an endoscopically unresectable lesion was detected [40.9%; n = 9/22], [ii] there was a deviation from the planned management pathway [40.9%; n = 9/22], such as service-, clinician- or patient-related delays in acting on a detected lesion, or [iii] lesions were potentially missed as they were typically located within areas of active inflammation or post-inflammatory change [36.4%; n = 8/22]., Conclusions: IBD PCCRC prevention will require more proactive strategies to reduce endoscopic inflammatory burden, and to improve lesion optical characterization, adherence to recommended surveillance intervals, and patient acceptance of prophylactic colectomy. However, the significant proportion appearing to originate from non-adenomatous-looking mucosa which fail to yield neoplasia on biopsy yet display aggressive cancer evolution highlights the limitations of current surveillance. Emerging molecular biomarkers may play a role in enhancing cancer risk stratification in future clinical practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive regimens. The aim of this retrospective single-center study was to investigate the incidence and implications of CMV DNAemia in KTRs with prior SOTs. The study included 97 KTRs with prior SOTs and 154 KTRs with no prior transplants as a control group. In the study group, the most common SOT before the current kidney transplantation (KT), was a previous KT. Patients in the KTR group with prior SOTs were more sensitized than those in the control group [calculated panel-reactive antibody > 30%: 49 (50.5%) vs. 30 (19.45%) patients, p  = 0.001]. There was a 39.2% incidence of CMV DNAemia in the previous SOT group compared to 48.7% in the control group [non-significant (NS)]. Patients with prior SOTs demonstrated a shorter post-transplant time to CMV DNAemia [median time 1.6 months (interquartile range, IQR 0.7-5.8) in the KTRs with prior SOTs vs. 2.6 months (IQR 1.5-8.1) in the control group ( p  = 0.001)]. Although the study highlights the need for tailored prophylaxis strategies and vigilant monitoring in KTRs with prior SOTs, its limitations, such as its retrospective nature and single-center design, call for further multicenter research to establish comprehensive guidelines for managing CMV DNAemia in this unique patient population. Despite these limitations, this study underscores the importance of recognizing the heightened risk of CMV infection or reactivation in KTRs overall and the potential benefits of proactive intervention to mitigate associated morbidity and mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Katz-Greenberg, Steinbrink, Shah and Byrns.)

Post-mastectomy pain syndrome (PMPS) is a syndrome broadly applied to the development of chronic pain after surgical breast intervention (i.e., lumpectomy and mastectomy). The incidence of PMPS is likely underreported, and this has contributed to a paucity of high-level evidence related to the treatment of the aforementioned condition. A drive to reduce the burden of opioid use has led to pain management physicians trialing a variety of strategies to help patients manage PMPS. This review discusses the latest evidence behind treatment options for PMPS, exploring medications as well as interventional techniques (e.g., nerve blocks, radiofrequency ablation, neuromodulation, and intrathecal drug delivery systems). Recent advances in neuromodulation technology are of particular interest here due to the well-localized nature of PMPS-related pain and the specificity with which modern neuromodulation techniques can generate an effect. Finally, the review proposes a framework with which to approach the care of patients with PMPS, with a specific emphasis on the early consideration of neuromodulation techniques along with functional and physical therapy to reduce patient medication burden and improve overall quality of life., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Shah et al.)

Objectives: A conservative hemoglobin transfusion threshold is noninferior to a liberal threshold in cardiac surgery. However, red blood cell (RBC) transfusion remains common during cardiac surgery. The authors' single-center, retrospective study aimed to decrease RBC transfusions for hemoglobin >7.5 g/dL in nonemergent cardiovascular surgeries utilizing cardiopulmonary bypass (CPB), by educating the anesthesiology and surgical staff on the benefits of a conservative threshold for transfusions, and incorporating the discussion and routine use of blood conservation methods for all nonemergent cardiac surgeries., Design: This was a single-center, retrospective study that included all nonemergent coronary artery bypass grafting and single-valve cases utilizing CPB from January 2018 to December 2021 before and after the intervention in July 2019., Setting: The data involved a single community hospital., Participants: A total of 417 patients were included in the study., Interventions: The authors adopted a conservative threshold for blood transfusion and implemented a collaborative multidisciplinary approach to blood conservation., Measurements and Main Results: Baseline patient characteristics were summarized, and the incidence of RBC transfusion before and after the intervention on July 26, 2019, were compared by Wilcoxon rank sum and chi-square tests. Multivariate logistic regression was used. The intervention was significantly associated with reduced RBC transfusion rate after adjusting for confounding variables (p < 0.05). The odds of receiving an RBC transfusion among patients after the intervention was 0.615 times the odds among patients before intervention (95% CI: 0.3913-0.9663)., Conclusions: The authors' goal was to improve patient outcomes and the quality of perioperative care during cardiac surgery. By implementing a protocol and educating anesthesiologists, surgeons, and perfusionists, they successfully decreased the incidence of RBC transfusion above a hemoglobin of 7.5 g/dL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Peripheral nerve blocks are becoming increasingly used as adjunctive treatment modalities for a variety of conditions refractory to medical management. Right or left stellate ganglion blocks (SGB) are a specific type of peripheral nerve block that target the sympathetic blockade of neuronal impulses using the injection of local anesthetic and steroids into nerve bundles in the cervical area. This review article is intended to summarize the common uses of stellate ganglion blocks and explain the procedural technique, which has evolved with technological advances in ultrasonography. The similarities between these disease processes are centered around sympathetic hyperactivity. This sympathetic overdrive state is created by increased levels of nerve growth factor (NGF), which causes a cascade of sympathetic sprouting resulting in increased norepinephrine (NE) systemically. Reversal of this cascade by local anesthetic injection into the stellate ganglion thereby reduces NGF and sympathetic sprouting subsequently lowering overall norepinephrine levels. This is the unifying theory by which SGB is able to provide resolution for the varied clinical conditions described in this article.  This review article discusses the physiology of several conditions where stellate ganglion blocks are being investigated as an adjunct treatment modality, including anosmia, PTSD, long-COVID, chronic fatigue syndrome, menopausal hot flashes, and ventricular tachyarrhythmias. Overall, the current literature supporting the use of stellate ganglion blocks for several esoteric conditions is limited; however, case reports to date have shown promising evidence-based results supporting their use as an adjunctive treatment among patients with refractory symptoms to existing treatment algorithms. In conclusion, SGB should be considered among patients with refractory symptoms for medical management in the conditions discussed in this article. Further research is needed to delineate which patients will benefit from the use of SGB, the use of subsequent blocks and timelines in between injections, and unilateral versus bilateral blockade., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kirkpatrick et al.)

Introduction Worldwide, diabetic retinopathy (DR) is one of the leading causes of vision loss. Early treatment and screening for DR have a major role in reducing the rate of the disease and the coronavirus disease 2019 (COVID-19) pandemic-related restrictions have altered real-world practice patterns in managing DR. Aims and objectives To evaluate the impact of the COVID-19 pandemic on the management of DR amongst patients presenting to a tertiary eye care center in Gujarat, India. Methods This is a cross-sectional study comparison of ophthalmic findings of 72 patients who presented to a tertiary care hospital with the manifestation of DR before and after the COVID-19 outbreak and subsequent lockdown. All the patients underwent detailed ophthalmic examinations, including optical coherence tomography (OCT) and fundus fluorescein angiography (FFA). Results The mean age of participants was 54.5 years, with the mean duration of diabetes being five years since first detected. Diabetes was present in 26 patients out of 72. The number of follow-up visits to an ophthalmologist before COVID-19 was at least every one to three months, which significantly decreased after the lockdown of COVID-19. We found a significant progression of DR and clinically significant macular edema (CSME) in patients with diabetes. Before COVID-19, there were two mild non-proliferative diabetic retinopathy (NPDR), seven moderate NPDR, 15 severe NPDR, and 15 very severe NPDR, which were increased post lockdown to three, nine, 27, and 21, respectively. The proliferative diabetic retinopathy (PDR) vitreous hemorrhage (VH) and tractional retinal detachment (TRD) were also increased to 12 after lockdown as compared to only six before the COVID-19 lockdown. The causes for progression are inability to attend regular check-ups, inability to take proper treatment of diabetes and DR, poor control of diabetes, episode of COVID-19, history of high dose of steroid use, poor kidney function, and not knowing that there is a progression of the disease. A common reason for not visiting an ophthalmologist was fear of the unknown due to COVID-19. Conclusions COVID-19 has severely impacted the routine follow-up of DR and, in the subsequent years, there might be an increased incidence of severe outcomes due to DR. The second wave of COVID-19 and its lockdown have had very significant effects on the visual outcome of untreated DR patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Prajapati et al.)

Background. Pediatric endodontics is a field with constant evolution, resulting in the shifting of paradigms from the use of conventional hand files to rotary files for biomechanical preparation in primary teeth. Biomechanical preparation plays a crucial role in the success of root canal treatment. Primary teeth need special attention since they differ from permanent teeth in root canal morphology. Cleaning and shaping of the canals damage the root dentin, leading to dentinal cracks. Newer techniques for root canal preparation, including Ni-Ti rotary files and SAF system, have been developed for use in pediatric endodontics to overcome the drawbacks of conventional methods. The present study compared dentinal defects formed by rotary systems in primary teeth. Methods. Eighty primary teeth were included. The teeth were decoronated with a diamond disc. All the roots were inspected for any pre-existing cracks or craze lines under transmitted light under a stereomicroscope. The specimens were then divided into four groups (n=20): group 1: control, group 2: hand files (HF), group 3: ProTaper files, and group IV: SAF files. The samples were instrumented according to the group they were assigned to. Results. The HF and SAF groups exhibited fewer microcracks. Dentinal microcracks were observed in roots prepared with rotary ProTaper files. There were significant differences between HF/SAF and rotary files ( P <0.05). Conclusion. Stainless steel hand K-files and SAF instruments resulted in fewer dentinal damage than the ProTaper Universal files. SAF exhibited satisfactory results with minimal or no crack formation., (© 2021 The Author(s).)

While a bidirectional positive link between palatable food intake and alcohol drinking has been suggested, several rodents studies report reduced alcohol drinking following palatable diets exposure. These studies utilized purified rodents' diets high in sugar/fat; however, the effects of hyper-palatable food (HPF) rich in fat and sugar on alcohol drinking remain unclear. Furthermore, neural substrates involved in HPF-mediated changes in alcohol consumption are poorly understood. Therefore, the present study evaluated the effects of patterned feeding of a hyper-palatable food (Oreo cookies) on alcohol drinking as well as dopamine (DA) and serotonin (5-HT) content in rat's mesocorticolimbic (medial-prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens) circuitry. Male Long Evans rats received 8-weeks of intermittent (Mon, Tue, Wed) Oreo cookies access, which induced a patterned feeding, in which rats in the Oreo group overconsumed calories on HPF days whereas underconsumption was observed on chow only (Thu, Fri) days. Following HPF exposure, alcohol consumption was evaluated while patterned feeding continued. Alcohol intake in the Oreo group was significantly lower as compared to the chow controls. However, alcohol intake in the Oreo group increased to the levels seen in the group receiving chow following the suspension of patterned HPF feeding. Finally, DA levels in the nucleus accumbens were significantly greater, whereas its metabolite (DOPAC) levels were lower in the Oreo group compared to the chow controls. Surprisingly, 5-HT levels remained unaltered in all tested brain areas. Together, these data suggest that HPF-associated increased DA availability and reduced DA turnover within mesocorticolimbic circuitry may regulate alcohol drinking following patterned HPF feeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Leon, Shah, Bailey, Karkhanis and Sirohi.)

Moderate to severe pain occurs in many cancer patients during their clinical course and may stem from the primary pathology, metastasis, or as treatment side effects. Uncontrolled pain using conservative medical therapy can often lead to patient distress, loss of productivity, shorter life expectancy, longer hospital stays, and increase in healthcare utilization. Various publications shed light on strategies for conservative medical management for cancer pain and a few international publications have reviewed limited interventional data. Our multi-institutional working group was assembled to review and highlight the body of evidence that exists for opioid utilization for cancer pain, adjunct medication such as ketamine and methadone and interventional therapies. We discuss neurolysis via injections, neuromodulation including targeted drug delivery and spinal cord stimulation, vertebral tumor ablation and augmentation, radiotherapy and surgical techniques. In the United States, there is a significant variance in the interventional treatment of cancer pain based on fellowship training. As a first of its kind, this best practices and interventional guideline will offer evidenced-based recommendations for reducing pain and suffering associated with malignancy., Competing Interests: MMA is a consultant for Abbott, Bioness, Vertos Medical. TD is a consultant for Abbott, Vertos, Axonics, Flowonix, SpineThera, Saluda Medical, Nalu, Medtronic, Nevro, SI Bone, Stimgenics, SPR Therapeutics, Cornerloc, Boston Scientific, PainTeq, Ethos, and Vertiflex. TD is a member of the advisory board for Abbott, Vertos, Flowonix, Nalu, SPR Therapeutics and Vertiflex. TD has stock options in Bioness, Vertiflex, Axonic, Vertos, SpineThera, Nalu, Cornerloc, PainTeq and SPR Therapeutics. TD has common stock in Saluda Medical. He is a research consultant for Abbott, Vertos, Mainstay Medical, Saluda Medical, SPR Therapeutics, Boston Scientific and Vertiflex. TD has a patent pending for the DRG paddle lead with Abbott. DS is a consultant for Flowonix, Medtronic, Merit, Abbott, Nevro, PainTeq, ans Vertos. JMH is a consultant for Abbott, Boston Scientific, and Nevro. SEB is a consultant for Medtronic. VS is a consultant for Releviate LLC. AG is a consultant for Medtronic, SPR therapeutics, Nalu Medical and serves on the Advisory Board for AIS HealthCare (advisory board) and Spark medical. NHS is a consultant for Abbott. JSW is a consultant for Abbott, Medtronic, Boston Scientific, Vertos, Saluda, PainTeq, Omnia Medical. Research Consultant for Abbott, Saluda. JHG is a consultant for Abbott and Stratus. JHG receives research support from SPR Therapeutics. AV is a consultant for CornerLoc, Vertos, Guidepoint Global. Research consultant for SPR. AEH is consultant for Abbott. AE is a consultant for Abbott, Boston Scientific, Medtronic, Nevro and Vertos Medical. KS is a consultant for Abbott, Boston Scientific, Flowonix, Nevro, Vertos Medical. JS is a consultant for Abbott labs, Executive leadership council for Vertos Medical, Shareholder and Medical Advisory Board for Celeri Health. SN is a consultant for Medtronic and AIS. The authors report no other conflicts of interest in this work., (© 2021 Aman et al.)

Visual analogue scales (VAS) have commonly been used to assess appetite in children 8 years and older; however, these tools have been considered unreliable for children 7 years old and under. The objective of this pilot study was to develop a picture-based appetite assessment (PBAA) tool for children aged 4-10 years and pilot test it compared to a VAS-based appetite assessment. The study hypothesis was that the PBAA scores would decrease following the consumption of an ad libitum snack compared to the scores in the fasted state in children 4 to 10 years old; furthermore, there would be a good level of agreement (intraclass correlation coefficients >0.75) between the appetite scores by the PBAA and VAS tools in children aged 8 years or older. At Visit 1, in a fasted state, all children (n = 15) completed the PBAA. Children who were 8-10 years old (n = 8) also completed the VAS-based appetite assessment. Then, an ad libitum snack was provided, and appetite assessments were repeated at 5-, 30- and 60-minutes post-snack. The same assessments were completed at visit 2 pre (fasting)- and post-consumption of a snack containing 25% of the amount consumed at visit 1 (limited snack). PBAA scores were different across time (P < .001) and between types of meal (ad libitum vs limited snack) (P = .015) in all children. A good agreement between the PBAA and VAS scores at 30 and 60 minutes after both types of meal was found (intraclass correlation coefficients >0.75). The PBAA tool was able to detect expected changes in appetite sensations and was in good agreement with the VAS instrument., (Copyright © 2021. Published by Elsevier Inc.)

Recent studies from our lab have demonstrated that intermittent high-fat diet access reduces alcohol drinking in rats. However, it was unclear if caloric overload, palatability, or diet itself triggered reduced alcohol drinking. It is also unknown if a similar paradigm could reduce relapse-like alcohol drinking. The presented study tested the hypothesis that acute intermittent palatable diet (PD) access would rescue relapse-like drinking and palatability, but not diet itself contributes to reduced drinking. Male Long Evans rats received six-weeks intermittent or chronic chow (controls) or PDs (high-fat diet, high-sugar diet) exposure, and alcohol testing occurred following PDs suspension. Alcohol intake was not significantly different among groups in either condition, suggesting that diet itself did not impact alcohol drinking. A subset of these rats received two-weeks intermittent PDs (Int-PDs) exposure and alcohol testing reinitiated while Int-PDs access continued. Alcohol intake significantly escalated (~137% compared to baseline; alcohol deprivation effect) in the chow controls, whereas it remained unchanged in PD groups. These data demonstrate the critical importance of acute intermittent PDs availability and its protective effect in relapse-like drinking. To assess the contribution of palatability in reduced alcohol drinking, a separate group of rats received two-weeks intermittent high-sugar diet (Int-HSD) or saccharin (Int-SAC) access and tested for alcohol drinking while Int-HSD/SAC continued. Alcohol drinking significantly decreased (~30%) in both HSD and SAC groups compared to the controls. These data identify the critical parameters by which acute intermittent PD access reduces alcohol drinking and could have important therapeutic implications in the management of alcoholism., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background The Transit Care Hub (TCH) is an inpatient ward traditionally used as a waiting area for patients who require transport to return home. In July 2018, a six-month pilot of a TCH pharmacist was funded to improve the flow of patients through the hospital. Setting Major Australian teaching hospital. Objective(s) To determine the effect that the TCH pharmacist had on patient flow within the hospital and on the time saved for other clinical pharmacists, as well as estimating cost savings. Methods A service delivery framework for the TCH pharmacist was developed and tested. This involved a proactive approach to patient discharge with ward-based staff. Data were collected from July to November 2018, 20 weeks prior to and 20 weeks after the commencement of the pilot. Main outcome measure Measurements included the number of best possible medication histories (BPMHs) completed during admission, improvements in arrival time to TCH from inpatient wards and cost savings. Results During the pilot study period (20 weeks), 791 patients were discharged by the TCH pharmacist, arriving an average of 70 minutes earlier than other patients discharging through TCH. There was a 16% increase in patients discharging through TCH which released ward beds. The TCH pharmacist increased the number of BPMHs on day of admission by 14%. There was an estimated annual saving of AU$252,008 for the hospital. Conclusions The TCH pharmacist service enhanced patient flow by coordinating earlier discharges, increasing the timely completion of BPMHs, and saving ward pharmacist time. Significant cost savings supported a permanently funded position.

Competing Interests: Competing interests: None declared.

We have previously shown that 6 weeks of intermittent high-fat diet (Int-HFD) pre-exposure significantly reduced alcohol drinking in rats, providing preliminary evidence of the effectiveness of a dietary intervention in reducing alcohol intake. However, the functional framework and underlying neurobiological mechanisms of such dietary intervention are unknown. Here, we examined the impact of Int-HFD pre-exposure duration on alcohol drinking, plasma feeding peptides, and central neurotransmitter receptors gene expression. Male Long Evans rats ( n = 6-7/group) received no pre-exposure, 1 or 2 weeks pre-exposure to Int-HFD and alcohol drinking (two-bottle choice) was evaluated. We observed HFD pre-exposure-dependent decrease in alcohol drinking, with a significant decrease observed following 2 weeks of Int-HFD pre-exposure. No significant between-group differences in plasma feeding peptides (i.e., ghrelin, leptin, insulin) were detected. A PCR array revealed that the expression of several neurotransmitter receptors was significantly ( p < 0.05 and ≥2-fold) altered in the striatum and ventral tegmental area compared to controls. These data suggest that pre-exposure to a palatable diet is critical to reduce alcohol drinking in rats, possibly through genetic alterations in the brain reward circuitry. Importantly, the present study is a step forward in identifying the critical framework needed to evaluate the therapeutic potential of nutritional contingency in the management of alcoholism.

Background and Aims: Epidural analgesia is believed to be the most difficult technique to learn for a trainee. The reason for this is not only inexperience of the provider and the complexity of the technique but also patient factors like obesity, spinal deformity and others which makes the epidural placement difficult. The aim of this study was to evaluate some of the common risk factors for difficult epidural placement as perceived by the anesthesia providers during training, with varying level of experience., Material and Methods: This prospective observational study includes patients who received epidural placement for labor analgesia. Data recorded on these patients included age, height, weight, body mass index (BMI), ease of palpation of the spinous process, level of epidural placement, number of attempts, time taken for epidural placement and experience of the provider. The association between the variables were assessed using logistic regression for first attempt success and Cox proportional hazard ratio for time to epidural placement., Results: A total of 373 patients received epidural placement for labor analgesia. The mean BMI at the time of placement was 34. The first attempt success rate for the placement of epidural was 67% ( n = 273). Women with well palpable spinous process were 3.3 times more likely to have a successful first attempt placement irrespective of the provider experience or BMI [3.39 (1.77-6.51), P < 0.001]. The time to placement was shorter in patients with good anatomical landmarks [1.58 (1.20-2.07), P < 0.001) and when performed by a trainee who had performed a minimum of 20 epidural procedures [1.57 (1.26-1.94), P < 0.001)., Conclusion: Inability to palpate the spinous process contributes to multiple attempts at epidural placement when performed by a trainee., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Anaesthesiology Clinical Pharmacology.)

Gastrointestinal (GI) microbiota are known to play paramount role in inflammatory bowel disease (IBD). Innovative sequencing methods have radically expanded our ability to analyze the intestinal microbiome. However, alterations of the GI microbiome in IBD have not yet been fully evaluated. Irregular colonization of the gut has been implicated in chronic intestinal inflammation. Faecal microbiota transplantation (FMT) is a procedure which aims to restore microbial disturbances to the individual's gut microbiome. The success of FMT in Clostridium difficile infection (CDI) has inspired studies to explore transplantation in other conditions such as IBD. Ulcerative colitis (UC) and Crohn's disease (CD), the two principal manifestations of IBD, are emerging as a worldwide epidemic and are multifactorial in aetiology. There have been various case series in the past looking at the use of FMT in IBD, with a large number of them focusing on UC; however, two new randomized controlled trials shed up-to-date light on the complex interactions between the GI microbiome and patients. Regardless of these new studies, much more remains unknown about the efficacy and safety profile of FMT in IBD, ultimately casting a shadow over its use as a therapeutic intervention in conditions other than CDI. Further researches are necessary to fully evaluate the role of FMT as a management option in IBD. In this review, we discuss and summarize the functions of FMT in IBD, and the relationship between IBD and the GI microbial variations present.

Despite the success of immune checkpoint blockade against melanoma, many "cold" tumors like prostate cancer remain unresponsive. We found that hypoxic zones were prevalent across preclinical prostate cancer and resisted T cell infiltration even in the context of CTLA-4 and PD-1 blockade. We demonstrated that the hypoxia-activated prodrug TH-302 reduces or eliminates hypoxia in these tumors. Combination therapy with this hypoxia-prodrug and checkpoint blockade cooperated to cure more than 80% of tumors in the transgenic adenocarcinoma of the mouse prostate-derived (TRAMP-derived) TRAMP-C2 model. Immunofluorescence imaging showed that TH-302 drives an influx of T cells into hypoxic zones, which were expanded by checkpoint blockade. Further, combination therapy reduced myeloid-derived suppressor cell density by more than 50%, and durably reduced the capacity of the tumor to replenish the granulocytic subset. Spontaneous prostate tumors in TRAMP transgenic mice, which completely resist checkpoint blockade, showed minimal adenocarcinoma tumor burden at 36 weeks of age and no evidence of neuroendocrine tumors with combination therapy. Survival of Pb-Cre4, Ptenpc-/-Smad4pc-/- mice with aggressive prostate adenocarcinoma was also significantly extended by this combination of hypoxia-prodrug and checkpoint blockade. Hypoxia disruption and T cell checkpoint blockade may sensitize some of the most therapeutically resistant cancers to immunotherapy.

Purpose: There are limited resources for long-term specialist follow-up after bariatric surgery. In selected centres, patients can access a postoperative support group, but there is no clear evidence to guide their delivery., Materials and Methods: A retrospective study of bariatric surgery patients ( n  = 152) who had been discharged from specialist follow-up (mean time since surgery 5.5 years), covering weight history, physical and psychosocial comorbidities, and the need for a postoperative bariatric support group., Results: Fifty-eight percent wanted a postbariatric surgery patient support group. This was not associated with operation type or the amount of weight lost or regained. However, those who wanted a support group were significantly more likely to be struggling to keep the weight off, to be unhappy with the way they look, or to be experiencing difficulties returning to work., Conclusions: These data point to an unmet patient requirement for a postoperative support group that is independent of weight loss success. More research is required to ascertain how such a group should be delivered, but our data would suggest that supporting patients with weight loss maintenance, body image, and return to work is an important part of postoperative care, and these needs extend well beyond the immediate period of specialist follow-up.

CD34+ cell selection minimizes graft-versus-host disease (GVHD) after haploidentical donor stem cell transplant but is associated with slow immune recovery and infections. We report a Phase I/II study of prophylactic donor lymphocyte infusion (DLI) followed by methotrexate (MTX) GVHD prophylaxis after CD34-selected haploidentical donor transplant. A prophylactic DLI was given between day +30 and +42. Rituximab was given with DLI for the last 10 patients. The goal of the study was to determine a DLI dose that would result in a CD4+ cell count > 100/µL at Day +120 in ≥ 66% of patients with ≤ 33% grade II-III, ≤ 17% grade III, and no grade IV acute GVHD by Day +180. Thirty-five patients with malignant (n = 25) or nonmalignant disease (n = 10) were treated after CD34-selected haploidentical donor peripheral blood stem cell transplant. The DLI dose of 5 × 10 4 /kg met the CD4/GVHD goal with 67% of patients having CD4+ cells > 100/µL and 11% grade II-IV acute GVHD. The cumulative incidence of chronic GVHD was 16%. Fatal viral and fungal infections occurred in 11%. The 2 year estimated overall survival was 69% and the relapse rate was 14% for patients in remission at transplant. There was no effect of NK alloreactivity on relapse. Nine of ten patients at the target DLI dose cohort of 5 × 10 4 /kg are alive with median follow-up of 18 mos (range 6-29). Delayed prophylactic DLI and MTX was associated with promising outcomes at the target DLI dose. This trial was registered at clinicaltrials.gov, # NCT01027702., (© 2017 Wiley Periodicals, Inc.)

Background: Physostigmine has long been recognized as an antidote to reverse anticholinergic delirium. However, its effectiveness, safety profile, and dosing have been disputed., Objectives: To describe effectiveness, adverse events, and dosing associated with the use of physostigmine to reverse anticholinergic delirium., Methods: A retrospective cohort study of hospitalized patients reported to a regional poison center system between 2003 and 2012 who received physostigmine to reverse an anticholinergic toxidrome. Data extraction of a priori defined variables were recorded with concurrence of investigators. The cases were stratified by the primary ingestant as the presumed causative agent and associations for response were performed using odds ratios (ORs), 95% confidence intervals (CI's), and p values., Results: Of the 1422 cases identified, 191 met the inclusion criteria. Patients exposed to non-diphenhydramine antihistamines (n = 14), antipsychotics (n = 4), and tricyclic antidepressants (n = 3) had 100% response to physostigmine, whereas anticholinergic plants (n = 46/67; 68.7%, OR: 0.70; CI: 0.36-1.35), diphenhydramine (n = 43/56; 64.2%, OR: 1.30; CI: 0.63-2.68), and combination products (n = 8/10; 80%, OR: 1.48; CI: 0.30-7.24) had partial response rates. Of the included patients, 142 (74.3%) were treated with physostigmine alone, and 16 (8.4%) of these patients were discharged directly from the emergency department (ED)., Discussion: Most patients, 182 (95.3%), had no documented adverse effects. Four patients (2.1%) experienced emesis, two experienced QTc prolongation (1.0%), and two experienced seizures (1.0%). There was a single fatality 6 h after physostigmine administration. Average initial total doses of physostigmine ranged from 1.0 to 1.75 mg. Most patients were admitted to the ICU (n = 110; 57.6%), however, 36 (18.8%) patients were discharged directly from the ED., Conclusions: In this retrospective cohort study, physostigmine administration to reverse anticholinergic delirium had a good safety profile, and often improved or resolved anticholinergic delirium when administered in doses less than 2 mg.

Most patients who could be cured of sickle cell disease (SCD) with stem cell transplantation do not have a matched sibling donor. Successful use of alternative donors, including mismatched family members, could provide a donor for almost all patients with SCD. The use of a reduced-intensity conditioning regimen may decrease late adverse effects. Ten patients with symptomatic SCD underwent CD34 + cell-selected, T-cell-depleted peripheral blood stem cell transplantation from a mismatched family member or unrelated donor. A reduced-intensity conditioning regimen including melphalan, thiotepa, fludarabine, and rabbit anti-thymocyte globulin was used. Patients were screened for a companion study for immune reconstitution that included a donor lymphocyte infusion given 30-42 days after transplant with intravenous methotrexate as graft-versus-host disease (GVHD) prophylaxis. Seven eligible patients were treated on the companion study. Nine of 10 patients are alive with a median follow-up of 49 months (range, 14-60 months). Surviving patients have stable donor hematopoietic engraftment (mean donor chimerism, 99.1% ± 0.7%). There were no sickle cell complications after transplant. Two patients had grade II-IV acute GVHD. One patient had chronic GVHD. Epstein-Barr virus-related posttransplant lymphoproliferative disorder (PTLD) occurred in 3 patients, and 1 patient died as a consequence of treatment of PTLD. Two-year overall survival was 90%, and event-free survival was 80%. A reduced-intensity conditioning regimen followed by CD34 + cell-selected, T-cell-depleted alternative donor peripheral blood stem cell transplantation achieved primary engraftment in all patients with a low incidence of GVHD, although PTLD was problematic. This trial was registered at clinicaltrials.gov as #NCT00968864., Competing Interests: Conflict-of-interest disclosure: The authors declare no competing financial interests.

A mismatch between fatty acid availability and utilization leads to cellular/organ dysfunction during cardiometabolic disease states (e.g., obesity, diabetes mellitus). This can precipitate cardiac dysfunction. The heart adapts to increased fatty acid availability at transcriptional, translational, post-translational and metabolic levels, thereby attenuating cardiomyopathy development. We have previously reported that the cardiomyocyte circadian clock regulates transcriptional responsiveness of the heart to acute increases in fatty acid availability (e.g., short-term fasting). The purpose of the present study was to investigate whether the cardiomyocyte circadian clock plays a role in adaptation of the heart to chronic elevations in fatty acid availability. Fatty acid availability was increased in cardiomyocyte-specific CLOCK mutant (CCM) and wild-type (WT) littermate mice for 9weeks in time-of-day-independent (streptozotocin (STZ) induced diabetes) and dependent (high fat diet meal feeding) manners. Indices of myocardial metabolic adaptation (e.g., substrate reliance perturbations) to STZ-induced diabetes and high fat meal feeding were found to be dependent on genotype. Various transcriptional and post-translational mechanisms were investigated, revealing that Cte1 mRNA induction in the heart during STZ-induced diabetes is attenuated in CCM hearts. At the functional level, time-of-day-dependent high fat meal feeding tended to influence cardiac function to a greater extent in WT versus CCM mice. Collectively, these data suggest that CLOCK (a circadian clock component) is important for metabolic adaption of the heart to prolonged elevations in fatty acid availability. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The genetic diversity of Human Immunodeficiency Virus type-1(HIV-1) has been shown to affect the performance of Nucleic Acid Testing (NAT) of Human Immunodeficiency Virus type-1. Although, majority NAT assays were designed to detect the conserved regions of HIV-1 mutations at the primer or probe binding regions may lead to false negatives. In this study, we evaluated the feasibility of detecting two genomic targets for enhanced sensitivity. A total of 180 tests using HIV-1 VQA RNA quantitation standard, 240 tests using EQAPOL HIV-1 viral diversity subtype panel, and 30 clinical plasma samples from Cameroon were evaluated. The analysis was based on probit and hit rate. The genomic targets LOD estimated by PROBIT for the gag target was 118 cps/ml (95%CI 64 cps/ml lower bound), Pol or POL/LTR was at 40 cps/ml (95%CI 17, 16 cps/ml), LTR 45 cps/ml (95%CI 20 cps/ml lower bound), and Gag/LTR at 67.8 cps/ml (95%CI 32 cps/ml lower bound). For HIV-1 subtypes the overall reactivity was 55-100% when tested at 100 and 1000 cps/ml and combination of genomic targets detection increased the reactivity to 100%. The plasma samples evaluation showed LTR or pol/LTR combination yielded higher sensitivity for patients with lower viral load (<40 cps/ml). We conclude that detection of two HIV-1 genomic targets improved sensitivity for detection of genetically diverse HIV-1 strains., (© 2015 Wiley Periodicals, Inc.)

Mesenchymal stem cells (MSCs) although used for bone tissue engineering are limited by the requirement of isolation and culture prior to transplantation. Our recent studies have shown that biomaterial implants can be engineered to facilitate the recruitment of MSCs. In this study, we explore the ability of these implants to direct the recruitment and the differentiation of MSCs in the setting of a bone defect. We initially determined that both stromal derived factor-1alpha (SDF-1α) and erythropoietin (Epo) prompted different degrees of MSC recruitment. Additionally, we found that Epo and bone morphogenetic protein-2 (BMP-2), but not SDF-1α, triggered the osteogenic differentiation of MSCs in vitro. We then investigated the possibility of directing autologous MSC-mediated bone regeneration using a murine calvaria model. Consistent with our in vitro observations, Epo-releasing scaffolds were found to be more potent in bridging the defect than BMP-2 loaded scaffolds, as determined by computed tomography (CT) scanning, fluorescent imaging and histological analyses. These results demonstrate the tremendous potential, directing the recruitment and differentiation of autologous MSCs has in the field of tissue regeneration., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Intracranial cerebral aneurysms in the pediatric population are infrequent, and those occurring in infants less than 1 year old are extremely rare. Of intracranial aneurysms in children, dissecting aneurysms are the most common type seen. While spontaneous dissecting aneurysms usually present with ischemia, hemorrhage can also occur., Methods: A retrospective review of our patients revealed that from July 1, 2007 to June 30, 2012, four infants were treated for ruptured distal dissecting intracranial aneurysms at Texas Children's Hospital. Mycotic aneurysms and collagen vascular disorder were excluded in all four cases. All patients presented in our series presented with subarachnoid hemorrhage, and three had intraventricular hemorrhage. All patients underwent conventional catheter angiography for diagnosis. All patients in this series were managed in the acute or subacute period with surgical or endovascular trapping without distal bypass procedures. All four patients tolerated sacrifice of the parent vessels feeding these distal aneurysms well., Case Report and Review of Literature: We describe the presentation and management of these rare cases and then review the current literature on the management of these dissecting aneurysms in infants.

Background/aims: Knowledge of dalbavancin renal replacement therapy (RRT) disposition is vital to ensure appropriate dosing. In vitro models of continuous RRT and intermittent hemodialysis (IHD) were used to determine dalbavancin transmembrane clearance (CLtm)., Methods: Dalbavancin saturation and sieving coefficients (SCs) were determined for hemodialysis and hemofiltration therapies, respectively, using various hemodiafilter and effluent rate combinations. Dalbavancin CLtm estimates were calculated from observed saturation and SCs., Results: Saturation and SCs for both modalities of continuous dialysis and hemofiltration and IHD with high permeability hemodiafilters were small. Nonetheless, during continuous RRT with high dialysate and ultrafiltration rates, dalbavancin CLtm (0.20-1.26 ml/min) matched and often exceeded literature-derived dalbavancin renal clearances. Dalbavancin CLtm was undetectable during IHD with low-permeability hemodialyzers, but with high-permeability hemodialyzers, substantial CLtm (1.90-2.43 ml/min) was noted., Conclusion: Dalbavancin CLtm is dependent on RRT modality, hemodiafilter, and effluent flow. Dalbavancin doses may need to be adjusted depending on RRT parameters.