The Safety of Incisional Hernia Surgical Repair in Patients ≥70 Years.

Introduction Incisional hernias (IHs) are common complications of abdominal surgery. Frailty and advancing age could be related to poor outcomes after surgical interventions, especially after operating on challenging surgical fields with adhesions and dense scars. This study assesses the safety of IH surgical repair in patients aged 70 years and above. Methods A retrospective analysis of all patients who had IH surgical repair on an emergency and elective basis at a district hospital in the UK. The cohort was categorised into group I (<70 years) and group II (≥70 years). A comparative analysis was conducted between these groups based on demographic data, comorbidities, hernia characteristics, operative data, and patient outcomes. Results This study encompassed 262 patients, with a mean age of 61.8 SD± 14.2 years, of whom 152 (58%) were females. Of these, group I comprised 173, and group II included 89 patients. Notably, group I exhibited a higher prevalence of morbid obesity, with 46 (28.8%) cases, as opposed to 12 (15.2%) in group II; p=0.021. Conversely, group II demonstrated a greater incidence of individuals with at least one comorbidity and chronic obstructive pulmonary disease (COPD) than group I, p=0.004 and 0.003, respectively. Fifty-five (32%) and 49 (29.3%) of group I had multiple defects and recurrent hernias compared to 24 (28.2%) and 16 (18.8%) in group II, p=0.541 and 0.071, respectively. The mean hospital stays were 5.5 ± 8.3 and 8.33 ± 18.7 days, and the mean durations of surgery were 131.6 ± 105.2 and 106.73 ± 74.22 minutes in groups I and II, p=0.057 and 0.181, respectively. No significant differences were observed in overall or wound-related complications, p=0.587 and 0.125. The rates of mortality within 30 days were three (1.7%) in group I and three (3.4%) in group II, with 90-day mortality rates at four (2.3%) and three (3.4%), respectively, indicating no significant difference. Similarly, no significant differences emerged between the groups regarding hernia recurrence rates (with a mean follow-up of 56 months) or 90-day readmission rates. Conclusions Surgical repair of IH is safe and effective in patients ≥70 years with comparable outcomes to younger patients.

Outcomes of Surgical Repair of Incisional Hernia in Patients With Severe and Morbid Obesity: A Comparative Study.

Introduction Incisional hernia (IH) is a common complication after open and minimal access abdominal surgery. The current practice guidelines recommend weight reduction to achieve a body mass index (BMI) < 35 kg/m2 before surgical repair of ventral hernias. However, this could be challenging to achieve, especially in emergency presentations. This study aims to assess the safety of surgical repair of IH in patients with BMI ≥35 kg/m2. Methods A retrospective comparative study has been conducted to include all patients who had surgical repair of IH on an elective and emergency basis in a UK District General Hospital. The patients were divided into two groups. Group I BMI < 35 kg/m2 and Group II with BMI ≥35 kg/m2. A comparison was made between the two groups according to demographics, comorbidities, hernia characteristics, operative data, and outcomes. Results The study included 239 patients, 181 in Group I and 58 in Group II. Morbid obesity was associated with male patients, and they were younger than Group I, p= 0.001 and 0.013, respectively. 13.8% of Group I had DM compared to 29.3% in Group II, p= 0.007. There were no significant differences in hernia characteristics or mode of surgery between the two groups. However, Group II had more overall and wound-related complications, p= <0.001 each. There were no significant differences in 30-day and 90-day mortality, recurrence rate, or 90-day readmissions. Conclusions Surgical repair of IH in patients with severe and morbid obesity is associated with more overall and wound-related complications.

Metformin has anti-inflammatory effects and induces immunometabolic reprogramming via multiple mechanisms in hidradenitis suppurativa.

BACKGROUND: Targeting immunometabolism has shown promise in treating autoimmune and inflammatory conditions. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving painful lesions in apocrine gland-bearing skin. Therapeutic options for HS are limited and often ineffective; thus, there is a pressing need for improved treatments. To date, metabolic dysregulation has not been investigated in HS. As HS is highly inflammatory, we hypothesized that energy metabolism is dysregulated in these patients. Metformin, an antidiabetic drug, which is known to impact on cellular metabolic and signalling pathways, has been shown to have anti-inflammatory effects in cancer and arthritis. While metformin is not licensed for use in HS, patients with HS taking metformin show improved clinical symptoms. OBJECTIVE: To assess the effect and mechanism of action of metformin in HS. METHODS: To assess the effect of metformin in vivo, we compared the immune and metabolic profiles of peripheral blood mononuclear cells (PBMCs) of patients with HS taking metformin vs. those not taking metformin. To examine the effect of metformin treatment ex vivo, we employed a skin explant model on skin biopsies from patients with HS not taking metformin, which we cultured with metformin overnight. We used enzyme-linked immunosorbent assays, multiplex cytokine assays and quantitative real-time polymerase chain reaction (RT-PCR) to measure inflammatory markers, and Seahorse flux technology and quantitative RT-PCR to assess glucose metabolism. RESULTS: We showed that metabolic pathways are dysregulated in the PBMCs of patients with HS vs. healthy individuals. In metformin-treated patients, these metabolic pathways were restored and their PBMCs had reduced inflammatory markers following long-term metformin treatment. In the skin explant model, we found that overnight culture with metformin reduced inflammatory cytokines and chemokines and glycolytic genes in lesions and tracts of patients with HS. Using in vitro assays, we found that metformin may induce these changes via the NLR family pyrin domain containing 3 (NLRP3) inflammasome and the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway, which is linked to glycolysis and protein synthesis. CONCLUSIONS: Our study provides insight into the mechanisms of action of metformin in HS. The anti-inflammatory effects of metformin support its use as a therapeutic agent in HS, while its effects on immunometabolism suggest that targeting metabolism is a promising therapeutic option in inflammatory diseases, including HS.

Waist to height ratio in nonalcoholic fatty liver disease - Systematic review and meta-analysis.

BACKGROUND AND AIMS: Current nonalcoholic fatty liver disease (NAFLD) guidelines do not provide any recommendations regarding the waist-to-height ratio (WHtR), a simple obesity metric calculated by dividing waist circumference by height. Therefore, we performed a systematic review and meta-analysis aiming to evaluate WHtR in NAFLD. METHODS: We performed a systematic electronic search on PubMed, Embase, and Scopus, identifying observational studies assessing WHtR in NAFLD. QUADAS-2 tool was used to evaluate the quality of included studies. The two main statistical outcomes were the area under the curve (AUC) and the mean difference (MD). RESULTS: We included a total of 27 studies in our quantitative and qualitative synthesis, with a total population of 93,536 individuals. WHtR was significantly higher in NAFLD patients compared to controls with an MD of 0.073 (95% CI 0.058 - 0.088). This was also confirmed after conducting a subgroup analysis according to the hepatic steatosis diagnosis method, for ultrasound (MD 0.066 [96% CI 0.051 - 0.081]) and transient elastography (MD 0.074 [96% CI 0.053 - 0.094]). Moreover, NAFLD male patients presented significantly lower WHtR compared to female patients (MD -0.022 [95% CI -0.041 - -0.004]). The AUC of WHtR for predicting NAFLD was 0.815 (95% CI 0.780 - 0.849). CONCLUSIONS: WHtR is considerably higher in NAFLD patients compared to controls. Female NAFLD patients present higher WHtR compared to NAFLD male patients. In comparison to other presently suggested scores and markers, the WHtR's accuracy in predicting NAFLD is considered acceptable.

Adiponectin Levels in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Adipose tissue plays an important role in the pathogenesis of inflammatory conditions. The role of adipokines in inflammatory bowel disease (IBD) has been evaluated in the current literature with conflicting results. The aim of this study was to evaluate adiponectin levels in IBD patients, including Crohn's disease (CD) and ulcerative colitis (UC), compared to controls, as well as further subgroup analyses. Hence, assessing the potential role of adiponectin as a surrogate marker. METHODS: We performed a systematic electronic search on PubMed, Embase, Scopus, and Cochrane Library, including observational or interventional studies evaluating serum or plasma adiponectin levels in IBD patients in humans. The primary summary outcome was the mean difference (MD) in serum or plasma adiponectin levels between IBD patients versus controls. Subgroup analyses were conducted involving adiponectin levels in CD and UC compared to controls, as well as CD compared to UC. RESULTS: A total of 20 studies were included in our qualitative synthesis and 14 studies in our quantitative synthesis, with a total population sample of 2,085 subjects. No significant MD in serum adiponectin levels was observed between IBD patients versus controls {-1.331 (95% confidence interval [CI]: -3.135-0.472)}, UC patients versus controls (-0.213 [95% CI: -1.898-1.472]), and CD patients versus controls (-0.851 [95% CI: -2.263-0.561]). Nevertheless, a significant MD was found between UC patients versus CD patients (0.859 [95% CI: 0.097-1.622]). CONCLUSIONS: Serum adiponectin levels were not able to differentiate between IBD, UC, and CD patients compared to controls. However, significantly higher serum adiponectin levels were observed in UC compared to CD patients.

Do Colonic Mucosal Tumor Necrosis Factor Alpha Levels Play a Role in Diverticular Disease? A Systematic Review and Meta-Analysis.

Diverticular disease (DD) is the most frequent condition in the Western world that affects the colon. Although chronic mild inflammatory processes have recently been proposed as a central factor in DD, limited information is currently available regarding the role of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). Therefore, we conducted a systematic review and meta-analysis aiming to assess the mucosal TNF-α levels in DD. We conducted a systematic literature search using PubMed, Embase, and Scopus to identify observational studies assessing the TNF-α levels in DD. Full-text articles that satisfied our inclusion and exclusion criteria were included, and a quality assessment was performed using the Newcastle-Ottawa Scale (NOS). The principal summary outcome was the mean difference (MD). The results were reported as MD (95% confidence interval (CI)). A total of 12 articles involving 883 subjects were included in the qualitative synthesis, out of which 6 studies were included in our quantitative synthesis. We did not observe statistical significance related to the mucosal TNF-α levels in symptomatic uncomplicated diverticular disease (SUDD) vs. the controls (0.517 (95% CI -1.148-2.182)), and symptomatic vs. asymptomatic DD patients (0.657 (95% CI -0.883-2.196)). However, the TNF-α levels were found to be significantly increased in DD compared to irritable bowel disease (IBS) patients (27.368 (95% CI 23.744-30.992)), and segmental colitis associated with diverticulosis (SCAD) vs. IBS patients (25.303 (95% CI 19.823-30.784)). Between SUDD and the controls, as well as symptomatic and asymptomatic DD, there were no significant differences in the mucosal TNF-α levels. However, the TNF-α levels were considerably higher in DD and SCAD patients than IBS patients. Our findings suggest that TNF-α may play a key role in the pathogenesis of DD in specific subgroups and could potentially be a target for future therapies.

Incisional Hernia: A Surgical Complication or Medical Disease?

Incisional hernia (IH) is a frequent complication following abdominal surgery. The development of IH could be more sophisticated than a simple anatomical failure of the abdominal wall. Reported IH incidence varies among studies. This review presented an overview of definitions, molecular basis, risk factors, incidence, clinical presentation, surgical techniques, postoperative care, cost, risk prediction tools, and proposed preventative measures. A literature search of PubMed was conducted to include high-quality studies on IH. The incidence of IH depends on the primary surgical pathology, incision site and extent, associated medical comorbidities, and risk factors. The review highlighted inherent and modifiable risk factors. The disorganisation of the extracellular matrix, defective fibroblast functions, and ratio variations of different collagen types are implicated in molecular mechanisms. Elective repair of IH alleviates symptoms, prevents complications, and improves the quality of life (QOL). Recent studies introduced risk prediction tools to implement preventative measures, including suture line reinforcement or prophylactic mesh application in high-risk groups. Elective repair improves QOL and prevents sinister outcomes associated with emergency IH repair. The watchful wait strategy should be reviewed, and options should be discussed thoroughly during patients' counselling. Risk stratification tools for predicting IH would help adopt prophylactic measures.

Structure, functions, performance and gaps of event-based surveillance (EBS) in Sudan, 2021: a cross-sectional review.

BACKGROUND: Event-based surveillance (EBS) is an essential component of Early Warning Alert and Response (EWAR) as per the International Health Regulations (IHR), 2005. EBS was established in Sudan in 2016 as a complementary system for Indicator-based surveillance (IBS). This review will provide an overview of the current EBS structure, functions and performance in Sudan and identify the gaps and ways forward.  METHODS: The review followed the WHO/EMRO guidelines and tools. Structured discussions, observation and review of records and guidelines were done at national and state levels. Community volunteers were interviewed through phone calls. Directors of Health Emergency and Epidemic Control, surveillance officers and focal persons for EBS at the state level were also interviewed. SPSS software was used to perform descriptive statistical analysis for quantitative data, while qualitative data was analysed manually using thematic analysis, paying particular attention to the health system level allowing for an exploration of how and why experiences differ across levels. Written and verbal consents were obtained from all participants as appropriate. RESULTS: Sudan has a functioning EBS; however, there is an underestimation of its contribution and importance at the national and states levels. The link between the national level and states is ad hoc or is driven by the need for reports. While community event-based surveillance (CEBS) is functioning, EBS from health facilities and from non-health sectors is not currently active. The integration of EBS into overall surveillance was not addressed, and the pathway from detection to action is not clear. The use of electronic databases and platforms is generally limited. Factors that would improve performance include training, presence of a trained focal person at state level, and regular follow-up from the national level. Factors such as staff turnover, income in relation to expenses and not having a high academic qualification (Diploma or MSc) were noticed as inhibiting factors. CONCLUSION: The review recommended revisiting the surveillance structure at national and state levels to put EBS as an essential component and to update guidelines and standard operation procedures SOPs to foster the integration between EBS components and the overall surveillance system. The need for strengthening the link with states, capacity building and re-addressing the training modalities was highlighted.

Atherogenic Index of Plasma in Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis.

(1) Background: Approximately a billion people worldwide are affected by NAFLD, which places a high clinical burden and financial cost on society. Liver biopsy is the gold standard for diagnosing NAFLD, but its invasivity limits the early diagnosis of NAFLD. Hence, it is important to look for alternate techniques in detecting and diagnosing NAFLD. NAFLD is associated with atherosclerosis. The purpose of this study was to assess the effectiveness of the atherogenic index of plasma (AIP) as a non-invasive modality for predicting NAFLD. (2) Methods: A search using electronic databases PubMed, EMBASE, and Scopus was carried out to find observational studies, looking at research that had been published up until the date of 11 May 2022. The included studies' quality, risk of bias, and internal validity were evaluated using the QUADAS-2 quality assessment tool. The key summary outcomes were the mean difference (MD) and area under the curve (AUC). (3) Results: A total of eight studies (81,178 participants) were included in our review, while 17% of the included participants had NAFLD. A sex distribution of 57.8% men and 42.2% women was observed. The AIP between NAFLD and the controls was not significant (MD 0.212 [95% CI 0.231-0.655]). A significant MD in AIP between the males and females with NAFLD was observed (MD 0.246 [95% CI 0.098-0.395]). The AIP predicted NAFLD with an AUC of 0.764 as well as in males (AUC 0.761) and females (AUC 0.733). (4) Conclusions: There was a substantial MD in the AIP between both sexes, but there was no significant difference in the AIP values between patients with NAFLD and the controls. The AIP is a reliable biomarker for the diagnosis of NAFLD since its ability to predict the development of NAFLD was comparable to that of the other biomarkers.

Chemerin Levels in Acute Coronary Syndrome: Systematic Review and Meta-Analysis.

OBJECTIVE: We evaluated the relevant published studies exploring the association between chemerin concentrations and acute coronary syndromes (ACSs). METHODS: A systematic search was performed in October 2021 using PubMed, Scopus, Embase, and Cochrane Library. We included full articles and assessed their quality using the Newcastle-Ottawa score. RESULTS: We found 6 studies in the systematic review and 5 of these were included in our meta-analysis. Mean difference (MD) of 41.69 ng/mL (95% CI, 10.07-73.30), 132.14 ng/mL (95% CI, -102.12-366.40), and 62.10 ng/mL (95% CI, 10.31-113.89) in chemerin levels was seen in ACS patients vs control subjects, ACS patients vs stable angina pectoris patients (SAP), and type 2 diabetes mellitus (T2DM) ACS patients vs nondiabetic ACS patients, respectively. CONCLUSION: Chemerin levels were significantly elevated in patients with ACS compared to controls, as well as in T2DM-ACS patients compared to nondiabetic ACS patients. However, no significant MD in chemerin levels was observed between SAP and ACS patients.

The NR4A agonist, Cytosporone B, attenuates pro-inflammatory mediators in human colorectal cancer tissue ex vivo.

Inflammation is a pivotal pathological factor in colorectal cancer (CRC) initiation and progression, and modulating this inflammatory state has the potential to ameliorate disease progression. NR4A receptors have emerged as key regulators of inflammatory pathways that are important in CRC. Here, we have examined the effect of NR4A agonist, Cytosporone B (CsnB), on colorectal tissue integrity and its effect on the inflammatory profile in CRC tissue ex vivo. Here, we demonstrate concentrations up 100 µM CsnB did not adversely affect tissue integrity as measured using transepithelial electrical resistance, histology and crypt height. Subsequently, we reveal through the use of a cytokine/chemokine array, ELISA and qRT-PCR analysis that multiple pro-inflammatory mediators were significantly increased in CRC tissue compared to control tissue, which were then attenuated with the addition of CsnB (such as IL-1ß, IL-8 and TNFα). Lastly, stratification of the data revealed that CsnB especially alters the inflammatory profile of tumours derived from males who had not undergone chemoradiotherapy. Thus, this study demonstrates that NR4A agonist CsnB does not adversely affect colon tissue structure or functionality and can attenuate the pro-inflammatory state of human CRC tissue ex vivo.

Acute Effects of Ketamine Infusion on Postoperative Mood Scores in Patients Undergoing Dilation and Curettage: A Randomized Double-Blind Controlled Study.

BACKGROUND: Emotional and psychological effects following abortion are more common than physical side effects and can range from mild regret to more serious complications such as depression. In the last decade, it has been suggested that low dose of ketamine is a fast-acting antidepressant. PURPOSE: The aim of this study was to investigate the impact of intraoperative ketamine infusion on postoperative mood score in patients undergoing Dilation and Curettage (D&C) under spinal anesthesia. We hypothesized that a single low-dose administration of ketamine infusion during D&C surgery can improve mood scores in the immediate postoperative period. METHODS: A prospective, randomized, double-blind, parallel-group, placebo-controlled trial. The study included a total of 60 patients, ≥18 years, physical status ASA II, with up to 12-week gestation undergoing elective D&C surgery. Patients were divided randomly into a ketamine group (group K) and a control group (group C). In group K, 0.4 mg/kg ketamine was given as a continuous infusion over 20 min intraoperatively. Main Outcome Measure. Profile of Mood States (POMS) was recorded preoperatively and 2 hours postoperatively. RESULTS: There were no differences in preoperative POMS between the two groups. Mean postoperative POMS of group K was lower than that of group C indicating mood improvement. Ketamine group patients showed higher sedation score and increased, although self-limiting, psychedelic phenomena than the control group. CONCLUSION: Observed data here support an acute effect of ketamine on mood but any further claim will be speculative. Further future studies exploring postoperative mood scores after 24 hours post-infusion are needed. This trial is registered with PACTR201907779292947.

Salcaprozate sodium (SNAC) enhances permeability of octreotide across isolated rat and human intestinal epithelial mucosae in Ussing chambers.

Octreotide is approved as a one-month injectable for treatment of acromegaly and neuroendocrine tumours. Oral delivery of the octapeptide is a challenge due mainly to low intestinal epithelial permeability. The intestinal permeation enhancer (PE) salcaprozate sodium (SNAC) has Generally Regarded As Safe (GRAS) status and is a component of an approved oral peptide formulation. The purpose of the study was to examine the capacity of salcaprozate sodium (SNAC), to increase its permeability across isolated rat intestinal mucosae from five regions and across human colonic mucosae mounted in Ussing chambers. Apical-side buffers were Kreb's-Henseleit (KH), fasted simulated intestinal fluid (FaSSIF-V2), rat simulated intestinal fluid (rSIF), and colonic simulated intestinal fluid (FaSSCoF). The basal apparent permeability coefficient (Papp) of [3H]-octreotide was equally low across rat intestinal regional mucosae in KH, rSIF, and FaSSIF-V2. Apical addition of 20 mM SNAC increased the Papp across rat tissue in KH: colon (by 3.2-fold) > ileum (3.4-fold) > upper jejunum (2.3-fold) > duodenum (1.4-fold) > stomach (1.4-fold). 20 mM and 40 mM SNAC also increased the Papp by 1.5-fold and 2.1-fold respectively across human colonic mucosae in KH. Transepithelial electrical resistance (TEER) values were reduced in the presence in SNAC especially in colonic regions. LC-MS/MS analysis of permeated unlabelled octreotide across human colonic mucosae in the presence of SNAC indicated that [3H]-octreotide remained intact. No gross damage was caused to rat or human mucosae by SNAC. Attenuation of the effects of SNAC was seen in rat jejunal mucosae incubated with FaSSIF-V2 and rSIF, and also to some extent in human colonic mucosae using FaSSCoF, suggesting interaction between SNAC with buffer components. In conclusion, SNAC showed potential as an intestinal permeation enhancer for octreotide, but in vivo efficacy may be attenuated by interactions with GI luminal fluid contents.

in Silico investigation of the structural requirements for the AMPA receptor antagonism by quinoxaline derivatives.

Glutamate receptors have been implicated in various neurological disorders and their antagonism offers a suitable approach for the treatment of such disorders. The field of drug design and discovery aims to find best medicines to prevent, treat and cure diseases quickly and efficiently. In this regard, computational tools have helped medicinal chemists modify and optimize molecules to potent drug candidates with better pharmacokinetic profiles, and guiding biologists and pharmacologists to explore new disease genes as well as novel drug targets. In the present study, to understand the structural requirements for AMPA receptor antagonism, molecular docking study was performed on 41 structurally diverse antagonists based on quinoxaline nucleus. Lamarckian genetic algorithm methodology was employed for docking simulations using AutoDock 4.2 program. The results obtained signify that the molecular docking approach is reliable and produces a good correlation coefficient (r(2) = 0.6) between experimental and docking predicted AMPA receptor antagonistic activity. The aromatic moiety of quinoxaline core has been proved to be vital for hydrophobic contacts exhibiting - interactions in docked conformations. However, polar moieties such as carboxylic group and 1,2,4-triazole moieties were noted to be sites for hydrophilic interactions in terms of hydrogen bonding with the receptor. These analyses can be exploited to design and develop novel AMPA receptor antagonists for the treatment of different neurological disorders.