Outcomes of laparoscopic modified Cellan-Jones repair versus open repair for perforated peptic ulcer at a community hospital.
Surgical endoscopy. 2023;(1):715-722
INTRODUCTION Minimally invasive or open Graham Patch repair remains the gold standard approach for management of perforated peptic ulcers (PPU). Herein, we report outcomes of laparoscopic technique and compare it with open approach at a community hospital. METHODS Retrospective observational study conducted comparing laparoscopic modified Cellan-Jones repair (mCJR) versus the standard open repair of PPU. Patients aged 18-90 years during 2016-2021 were offered either a minimally invasive or open approach depending on surgeon laparoscopic capability, and were compared in terms of demographics, co-morbidities, intra-operative details, and short-term outcomes. RESULTS A total of 49 patients were included (46.9% males, mean age 52.9 years, mean BMI 25.0, ASA ≥ III 75.5%, 75.5% smokers, 26.5% current NSAIDs use, and 71.4% alcohol drinkers). Duodenum was the most common perforation site (57.1%), and majority of ulcers were 1-2 cm (72.9%). Laparoscopic approach was performed in 16 consecutive patients (32.7%) by a single surgeon, with no conversions. Preoperative characteristics were similar for both groups. Compared to open approach, laparoscopic group were taken to operation immediately (< 4 h) (87.5% vs. 15.2%, p < 0.001), had lower estimated blood loss (11.8 ml vs. 73.8 ml, p = 0.063), and longer operative time (117.1 min vs. 85.6 min, p = 0.010). Postoperatively, nasogastric tube was removed earlier in laparoscopic group (POD1-2, 87.5% vs. 24.2%, p = 0.001), with earlier resumption of diet (POD1-2, 62.6% vs. 9.1%, p = 0.002), less narcotic usage (< 3 days, 58.3% vs. 6.1%, p < 0.001), earlier return of bowel function (POD1-2, 43.8% vs. 9.1%, p = 0.003) and shorter length of stay (LOS) (3.7 days vs. 16.1 days, p < 0.001). Both in-house mortality and morbidity rates were lower in the laparoscopic group, but not statistically significant [(0% vs. 6.1%, p = 0.347) and (12.5% vs. 39.4%, p = 0.500), respectively]. CONCLUSION Laparoscopic mCJR is a feasible method for repair of PPU, and it is associated with shorter LOS, and less narcotics usage in comparison to the open repair approach.
COVID-19: Reducing the risk via diet and lifestyle.
Journal of integrative medicine. 2023;(1):1-16
This review shows that relatively simple changes to diet and lifestyle can significantly, and rapidly, reduce the risks associated with coronavirus disease 2019 (COVID-19) in terms of infection risk, severity of disease, and even disease-related mortality. A wide range of interventions including regular exercise, adequate sleep, plant-based diets, maintenance of healthy weight, dietary supplementation, and time in nature have each been shown to have beneficial effects for supporting more positive health outcomes with COVID-19, in addition to promoting better overall health. This paper brings together literature from these areas and presents the argument that non-pharmaceutical approaches should not be overlooked in our response to COVID-19. It is noted that, in several cases, interventions discussed result in risk reductions equivalent to, or even greater than, those associated with currently available vaccines. Where the balance of evidence suggests benefits, and the risk is minimal to none, it is suggested that communicating the power of individual actions to the public becomes morally imperative. Further, many lives could be saved, and many harms from the vaccine mandates avoided, if we were willing to embrace this lifestyle-centred approach in our efforts to deal with COVID-19.
Somatic growth in single ventricle patients: A systematic review and meta-analysis.
Acta paediatrica (Oslo, Norway : 1992). 2023;(2):186-199
AIM: To map somatic growth patterns throughout Fontan palliation and summarise evidence on its key modifiers. METHODS Databases were searched for relevant articles published from January 2000 to December 2021. Height and weight z scores at each time point (birth, Glenn procedure, Fontan procedure and >5 years after Fontan completion) were pooled using a random effects meta-analysis. A random effects meta-regression model was fitted to model the trend in z scores over time. RESULTS Nineteen studies fulfilled eligibility criteria, yielding a total of 2006 participants. The z scores for height and weight were markedly reduced from birth to the interstage period, but recovered by about 50% following the Glenn procedure. At >10 years after the Fontan procedure, the z scores for weight seemed to normalise despite persistent lower height, resulting in increased body mass index. The review revealed a number of modifiers of somatic growth, including aggressive nutritional management, timing of Glenn/Fontan, prompt resolution of complications and obesity prevention programmes in adolescence and adulthood. CONCLUSION This review mapped the somatic growth of single ventricle patients and summarised key modifiers that may be amendable to improvement. These data provide guidance on strategies to further optimise somatic growth in this population and may serve as a benchmark for clinical follow-up.
Microbiota-immune-brain interactions: A lifespan perspective.
Current opinion in neurobiology. 2023;:102652
There is growing appreciation of key roles of the gut microbiota in maintaining homeostasis and influencing brain and behaviour at critical windows across the lifespan. Mounting evidence suggests that communication between the gut and the brain could be the key to understanding multiple neuropsychiatric disorders, with the immune system coming to the forefront as an important mechanistic mediator. Throughout the lifespan, the immune system exchanges continuous reciprocal signals with the central nervous system. Intestinal microbial cues alter immune mediators with consequences for host neurophysiology and behaviour. Several factors challenge the gut microbiota composition, which in response release molecules with neuro- and immuno-active potential that are crucial for adequate neuro-immune interactions. In this review, multiple factors contributing to the upkeep of the fine balance between health and disease of these systems are discussed, and we elucidate the potential mechanistic implications for the gut microbiota inputs on host brain and behaviour across the lifespan.
Overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAFV600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study.
The Lancet. Oncology. 2023;(1):33-44
BACKGROUND Primary analysis of the phase 3 IMspire150 study showed improved investigator-assessed progression-free survival with first-line atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) versus placebo, vemurafenib, and cobimetinib (control group) in patients with BRAFV600 mutation-positive melanoma. With a median follow-up of 18·9 months (IQR 10·4-23·8) at the primary analysis, overall survival data were immature. Here, we report the results from the second, prespecified, interim overall survival analysis. METHODS The multicentre, double-blind, placebo-controlled, randomised, phase 3 IMspire150 study was done at 108 academic and community hospitals in 20 countries. Patients aged 18 years or older with previously untreated unresectable stage IIIc or stage IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients were randomly assigned (1:1) to receive either atezolizumab (840 mg intravenously on day 1 and 15) or placebo plus vemurafenib (960 mg or 720 mg twice daily orally) and cobimetinib (60 mg once daily orally; 21 days on and 7 days off) in 28-day cycles. Atezolizumab and placebo were added to treatment regimens from cycle two onwards. Randomisation was done centrally (Durham, NC, USA) based on a permuted block randomisation scheme (block size of 4) using an interactive web-based response system and was stratified by geographical region and baseline lactate dehydrogenase concentration. Overall survival was analysed in the intention-to-treat population and safety was analysed in all patients who received at least one dose of study drug according to actual treatment received. The primary endpoint was investigator-assessed progression-free survival, which was previously reported. Here, we report the second, prespecified, interim overall survival analysis, which was planned after about 270 overall survival events had occurred. The trial is ongoing, but is no longer enrolling patients, and it is registered with ClinicalTrials.gov, NCT02908672. FINDINGS Between Jan 13, 2017, and April 26, 2018, 514 patients (median age 54 years [IQR 43-63]; 299 [58%] men and 215 [42%] women) were enrolled in the trial and randomly assigned to the atezolizumab group (256 [50%] patients) or the control group (258 [50%] patients). At the data cutoff (Sept 8, 2021), 273 patients had died (126 in the atezolizumab group and 147 in the control group). Median follow-up was 29·1 months (IQR 10·1-45·4) for the atezolizumab group versus 22·8 months (10·6-44·1) for the control group. Median overall survival was 39·0 months (95% CI 29·9-not estimable) in the atezolizumab group versus 25·8 months (22·0-34·6) in the control group (HR 0·84 [95% CI 0·66-1·06]; p=0·14). The most common adverse events of any grade in the atezolizumab group were blood creatine phosphokinase increased (123 [53%] of 231 patients), diarrhoea (116 [50%]), and pyrexia (115 [50%]). The most common adverse events of any grade in the control group were diarrhoea (157 [56%] of 280 patients), blood creatine phosphokinase increased (135 [48%]), and rash (119 [43%]). The most common grade 3-4 adverse events were increased lipase (54 [23%] of 231 patients in the atezolizumab group vs 62 [22%] of 280 patients in the control group), increased blood creatine phosphokinase (51 [22%] vs 50 [18%]), and increased alanine aminotransferase (32 [14%] vs 26 [9%]). Serious adverse events were reported in 112 (48%) patients in the atezolizumab group and 117 (42%) patients in the control group. Grade 5 adverse events were reported in eight (3%) patients in the atezolizumab group versus six (2%) patients in the control group. Two grade 5 adverse events (hepatitis fulminant and hepatic failure) in the atezolizumab group were considered to be associated with the triplet combination, and one event in the control group (pulmonary haemorrhage) was considered to be associated with cobimetinib. INTERPRETATION Additional follow-up of the IMspire150 trial showed that overall survival was not significantly improved with atezolizumab, vemurafenib, and cobimetinib compared with placebo, vemurafenib, and cobimetinib in patients with BRAFV600 mutation-positive advanced melanoma. Results of the final analysis are awaited to establish whether a significant improvement in overall survival can be achieved with long-term treatment with this triplet combination versus vemurafenib plus cobimetinib. FUNDING F Hoffmann-La Roche.
New mescaline-related N-acylhydrazone and its unsubstituted benzoyl derivative: Promising metallophores for copper-associated deleterious effects relief in Alzheimer's disease.
Journal of inorganic biochemistry. 2023;:112033
Alzheimer's disease (AD) is related to the presence of extracellular aggregated amyloid-β peptide (Aβ), which binds copper(II) with high affinity in its N-terminal region. In this sense, two new 1-methylimidazole-containing N-acylhydrazonic metallophores, namely, X1TMP and X1Benz, were synthesized as hydrochlorides and characterized. The compound X1TMP contains the 3,4,5-trimethoxybenzoyl moiety present in the structure of mescaline, a natural hallucinogenic protoalkaloid that occurs in some species of cacti. Single crystals of X1Benz, the unsubstituted derivative of X1TMP, were obtained. The experimental partition coefficients of both compounds were determined, as well as their apparent affinity for Cu2+ in aqueous solution. Ascorbate consumption assays showed that these N-acylhydrazones are able to lessen the production of ROS by the Cu(Aβ)-system, and a short-time scale aggregation study, measured through turbidity and confirmed by TEM images, revealed their capacity in preventing Aβ fibrillation at equimolar conditions in the presence and absence of copper. 1H15N HSQC NMR experiments demonstrated a direct interaction between Aβ and X1Benz, the most soluble of the compounds. The Cu2+ sequestering potential of this hydrazone towards Aβ was explored by 1H NMR. Although increasing amounts of X1Benz were unexpectedly not efficient at removing the metal-induced perturbations in Aβ backbone amides, the broadening effects observed on the compound's signals indicate the formation of a ternary Aβ‑copper-X1Benz species, which can be responsible for the observed ROS-lessening and aggregation-preventing activities. Overall, the N-acylhydrazones X1TMP and X1Benz have shown promising prospects as agents for the treatment of AD.
Short-term complications and post-acute sequelae in hospitalized paediatric patients with COVID-19 and obesity: A multicenter cohort study.
Pediatric obesity. 2023;(2):e12980
BACKGROUND Obesity increases the severity of coronavirus disease 2019 illness in adults. The role of obesity in short-term complications and post-acute sequelae in children is not well defined. OBJECTIVE To evaluate the relationship between obesity and short-term complications and post-acute sequelae of SARS-CoV-2 infection in hospitalized paediatric patients. METHODS An observational study was conducted in three tertiary hospitals, including paediatric hospitalized patients with a confirmatory SARS-CoV-2 RT-PCR from March 2020 to December 2021. Obesity was defined according to WHO 2006 (0-2 years) and CDC 2000 (2-20 years) growth references. Short-term outcomes were intensive care unit admission, ventilatory support, superinfections, acute kidney injury, and mortality. Neurological, respiratory, and cardiological symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms were considered as post-acute sequalae. Adjusted linear, logistic regression and generalized estimating equations models were performed. RESULTS A total of 216 individuals were included, and 67 (31.02%) of them had obesity. Obesity was associated with intensive care unit admission (aOR = 5.63, CI95% 2.90-10.94), oxygen requirement (aOR = 2.77, CI95% 1.36-5.63), non-invasive ventilatory support (aOR = 6.81, CI95% 2.11-22.04), overall superinfections (aOR = 3.02 CI95% 1.45-6.31), and suspected bacterial pneumonia (aOR = 3.00 CI95% 1.44-6.23). For post-acute sequalae, obesity was associated with dyspnea (aOR = 9.91 CI95% 1.92-51.10) and muscle weakness (aOR = 20.04 CI95% 2.50-160.65). CONCLUSIONS In paediatric hospitalized patients with COVID-19, severe short-term outcomes and post-acute sequelae are associated with obesity. Recognizing obesity as a key comorbidity is essential to develop targeted strategies for prevention of COVID-19 complications in children.
The role of sulfur nutrition in plant response to metal(loid) stress: Facilitating biofortification and phytoremediation.
Journal of hazardous materials. 2023;(Pt B):130283
Metal(loid)s contamination poses a serious threat to ecosystem biosafety and human health. Phytoremediation is a cost-effective and eco-friendly technology with good public acceptance, although the process does require a significant amount of time for success. To enhance the phytoremediation efficiency, numerous approaches have been explored, including soil amendments application with chelators to facilitate remediation. Sulfur (S), a macronutrient for plant growth, plays vital roles in several metabolic pathways that can actively affect metal(loid)s phytoextraction, as well as attenuate metal(loid) toxicity. In this review, different forms of S-amendments (fertilizers) on uptake and translocation in plants upon exposure to various metal(loid) are evaluated. Possible mechanisms for S application alleviating metal(loid) toxicity are documented at the physiological, biochemical and molecular levels. Furthermore, this review highlights the crosstalk between S-assimilation and other biomolecules, such as phytohormones, polyamines and nitric oxide, which are also important for metal(loid) stress tolerance. Given the effectiveness and potential of S amendments on phytoremediation, future studies should focus on optimizing phytoremediation efficiency in long-term field studies and on investigating the appropriate S dose to maximize the food safety and ecosystem health.
Consensus for experimental design in electromyography (CEDE) project: Single motor unit matrix.
Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology. 2023;:102726
The analysis of single motor unit (SMU) activity provides the foundation from which information about the neural strategies underlying the control of muscle force can be identified, due to the one-to-one association between the action potentials generated by an alpha motor neuron and those received by the innervated muscle fibers. Such a powerful assessment has been conventionally performed with invasive electrodes (i.e., intramuscular electromyography (EMG)), however, recent advances in signal processing techniques have enabled the identification of single motor unit (SMU) activity in high-density surface electromyography (HDsEMG) recordings. This matrix, developed by the Consensus for Experimental Design in Electromyography (CEDE) project, provides recommendations for the recording and analysis of SMU activity with both invasive (needle and fine-wire EMG) and non-invasive (HDsEMG) SMU identification methods, summarizing their advantages and disadvantages when used during different testing conditions. Recommendations for the analysis and reporting of discharge rate and peripheral (i.e., muscle fiber conduction velocity) SMU properties are also provided. The results of the Delphi process to reach consensus are contained in an appendix. This matrix is intended to help researchers to collect, report, and interpret SMU data in the context of both research and clinical applications.
Untargeted metabolomic approaches in food authenticity: A review that showcases biomarkers.
Food chemistry. 2023;:133856
The assessment of food authenticity is a topic that gained a lot of interest at the international level. This term includes misidentification of variety, origin, production system, processing but also adulteration. These frauds all have an analytical component, and research tends to offer new analytical solutions to manage them. One of them is non-targeted approaches, which get around the limitations of targeted analysis by detecting the unexpected. A wide range of products are studied such as wine, rice, olive oil, spices, and honey among the top five. Geographic origin is by far the fraud with the most attention. The main reason is probably the complexity to consider terroir effect and every other variable to determine an area of production. This review offers an overview of the potential of non-targeted analysis to assess food authenticity. These results also illustrate the capability to look for environmental terroir markers that could be cross-matrixes.