Prevalence of, Subtypes of, and the Role of Age in Incidental Appendiceal Neoplasms in Acute Appendicitis: A Single-Institute Study from Bahrain.

INTRODUCTION: Primary appendiceal neoplasms (ANs) are rare entities that can present with acute appendicitis symptoms. Accurate diagnosis of these diverse subtypes is crucial for prognosis and proper management. AIMS AND OBJECTIVES:  This descriptive retrospective study aims to determine the prevalence and pathological subtypes of incidental ANs in patients presenting with acute appendicitis symptoms at Salmaniya Medical Center (SMC) in Bahrain between the period of January 2020 and March 2024. Particular focus was placed on investigating whether advanced age is a significant risk factor for these neoplasms. MATERIALS AND METHODS:  The study included 38,643 patients (aged 15 years and above) who underwent appendectomy for suspected acute appendicitis during the study period. Demographic data, clinical diagnoses, preoperative imaging findings, histopathological reports, and management details were analyzed. Medical records of patients were retrieved from ISEHA system. Statistical analysis was done using Microsoft Excel. RESULTS: The results showed that 12 patients (0.04% per year) had different subtypes of appendiceal tumors. Neuroendocrine tumors were the most common, identified in nine patients (75%), including nine cases of well-differentiated neuroendocrine carcinoma (NEC). Other histopathological subtypes included low-grade appendiceal mucinous neoplasm (LAMN), adenocarcinoma, and goblet cell adenocarcinoma, each found in one patient. Additionally, two patients had confirmed appendiceal mucocele. The mean age of patients with ANs was 30 years (range: 19-52 years), and 66.6% were younger than 38 years.  Conclusion: These findings highlight the importance of considering ANs in the differential diagnosis of acute appendicitis, especially in older patients. Further research is warranted to confirm the role of age as a risk factor and guide clinical decision-making.

Low delayed bleeding and high complete closure rate of mucosal defects with the novel through-the-scope dual-action tissue clip after endoscopic resection of large nonpedunculated colorectal lesions (with video).

BACKGROUND AND AIMS: Complete closure after endoscopic resection of large nonpedunculated colorectal lesions (LNPCLs) can reduce delayed bleeding but is challenging with conventional through-the-scope (TTS) clips alone. The novel dual-action tissue (DAT) clip has clip arms that open and close independently of each other, facilitating tissue approximation. We aimed to evaluate the rate of complete closure and delayed bleeding with the DAT clip after endoscopic resection of LNPCLs. METHODS: This was a multicenter prospective cohort study of all patients who underwent defect closure with the DAT clip after EMR or endoscopic submucosal dissection (ESD) of LNPCLs ≥20 mm from July 2022 to May 2023. Delayed bleeding was defined as a bleeding event requiring hospitalization, blood transfusion, or any intervention within 30 days after the procedure. Complete closure was defined as apposition of mucosal defect margins without visible submucosal areas <3 mm along the closure line. RESULTS: One hundred seven patients (median age, 64 years; 42.5% women) underwent EMR (n = 63) or ESD (n = 44) of LNPCLs (median size, 40 mm; 74.8% right-sided colon) followed by defect closure. Complete closure was achieved in 96.3% (n = 103) with a mean of 1.4 ± .6 DAT clips and 2.9 ± 1.8 TTS clips. Delayed bleeding occurred in 1 patient (.9%) without requiring additional interventions. CONCLUSIONS: The use of the DAT clip in conjunction with TTS clips achieved high complete defect closure after endoscopic resection of large LNPCLs and was associated with a .9% delayed bleeding rate. Future comparative trials and formal cost-analyses are needed to validate these findings. (Clinical trial registration number: NCT05852457.).

Outcomes of Cold Snare Endoscopic Mucosal Resection of Nonampullary Duodenal Adenomas ≥1 cm: A Multicenter Study.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) with use of electrocautery (conventional EMR) has historically been used to remove large duodenal adenomas, however, use of electrocautery can predispose to adverse events including delayed bleeding and perforation. Cold snare EMR (cs-EMR) has been shown to be safe and effective for removal of colon polyps, but data regarding its use in the duodenum is limited. The aim of this study is to evaluate the efficacy and safety of cs-EMR for nonampullary duodenal adenomas ≥1 cm. METHODS: This was a multicenter retrospective study of patients with nonampullary duodenal adenomas ≥1 cm who underwent cs-EMR between October 2014 and May 2023. Patients who received any form of thermal therapy were excluded. Primary outcomes were technical success and rate of recurrent adenoma. Secondary outcomes were adverse events and predictors of recurrence. RESULTS: A total of 125 patients underwent resection of 127 nonampullary duodenal adenomas with cs-EMR. Follow up data was available in 89 cases (70.1%). The recurrent adenoma rate was 31.5% (n=28). Adverse events occurred in 3.9% (n=5) with four cases of immediate bleeding (3.1%) and one case of delayed bleeding (0.8%). There were no cases of perforation. The presence of high-grade dysplasia was found to be an independent predictor of recurrence (OR: 10.9 [95% CI: 1.1-102.1], p=0.036). CONCLUSION: This retrospective multicenter study demonstrates that cs-EMR for nonampullary duodenal adenomas is safe and technically feasible with an acceptable recurrence rate. Future prospective studies are needed to directly compare outcomes of cs-EMR with conventional and underwater EMR.

Multitargeted inhibitory effect of Mitoxantrone 2HCl on cervical cancer cell cycle regulatory proteins: a multitargeted docking-based MM\GBSA and MD simulation study.

Cervical cancer remains a significant global health concern that starts in the cervix, the lower part of the uterus that connects to the vagina and is caused by the human papillomavirus (HPV), necessitating the development of effective multitargeted effective and resistance-proof therapies. In early-stage cervical cancer may not show any symptoms, however, as the cancer progresses, some people may experience- abnormal vaginal bleeding, watery or bloody vaginal discharge, pain in the pelvis or lower back, pain during sex, and frequent and painful urination. In this study, we screened the complete FDA-approved drug library using a multitargeted inhibitory approach against four cervical cancer proteins, namely mitotic arrest deficient -2, DNA polymerase epsilon B-subunit, benzimidazole-related -1, and threonine-protein kinase-1 which crucially plays its role for the in its development process. We employed the HTVS, SP and XP algorithms for efficient filtering and screening that helped to identify Mitoxantrone 2HCl against all of them with docking and MM\GBSA scores ranging from - 11.63 to - 7.802 kcal/mol and - 74.38 to - 47.73 kcal/mol, respectively. We also evaluated the interaction patterns of each complex and the pharmacokinetics properties that helped gain insight into interactions. Subsequently, we performed multiscale MD simulations for 100 ns to understand the dynamic behaviour and stability of the Mitoxantrone 2HCl -protein complexes that revealed the formation of stable drug-protein complexes and provided insights into the molecular interactions that contribute to Mitoxantrone's inhibitory effects on these proteins and can be a better drug for cervical cancer. However, experimental studies of these findings could pave the way for therapies to combat cervical cancer effectively.

A Comprehensive Review on Cancer Vaccines and Vaccine Strategies in Hepatocellular Carcinoma.

HCC, the most prevalent form of primary liver cancer, presents a substantial global health challenge due to its high mortality and limited therapeutic options. This review delves into the potential of cancer vaccines as a novel therapeutic avenue for HCC. We examine the various categories of cancer vaccines, including peptide-based, dendritic cell-based, viral vector-based, DNA, and mRNA vaccines, and their potential application in HCC management. This review also addresses the inherent challenges in vaccine development, such as tumor heterogeneity and the need for identifying tumor-specific antigens. We underscore the role of cancer vaccines in reshaping the immune environment within HCC, fostering durable immune memory, and their potential in combination therapies. The review also evaluates clinical trials and emphasizes the necessity for more extensive research to optimize vaccine design and patient selection criteria. We conclude with future perspectives, highlighting the significance of personalized therapies, innovative antigen delivery platforms, immune modulatory agents, and predictive biomarkers in revolutionizing HCC treatment. Simple Summary: This review explores the potential of cancer vaccines as a promising therapeutic strategy for hepatocellular carcinoma (HCC), a prevalent and deadly liver cancer. The authors discuss various types of cancer vaccines, their challenges, and their role in modulating the immune response within HCC. They also highlight clinical trials and future perspectives, emphasizing the importance of personalized therapies, novel antigen delivery platforms, and predictive biomarkers. The findings from this research could significantly impact the research community by providing a comprehensive understanding of the current state of cancer vaccines for HCC, thereby guiding future research and potentially transforming HCC treatment strategies.

Mometasone Furoate Use for Recurrent Adenoid Hypertrophy: Randomized Controlled Clinical Trial.

Background& Objective: Adenoid hypertrophy (AH) in children is one of the most causes of nasal obstruction and is associated with many nasal and respiratory symptoms. Till now, surgery is the main option for managing the associated symptom of AH. The intranasal steroid has an effective role in the control of allergic rhinitis and associated AH. This work aimed to assess the effects of local mometasone on recurrent AH in children. Patients& Methods: A randomized controlled trial enrolled 39 patients aged between 2 and 15 years with recurrent AH. Those patients were randomly subdivided into three groups; group (A) received topical mometasone furoate (MF), group (B) did not receive any medication, and group (C) received topical normal saline. All groups were followed up for 8 weeks. Results: Patients who received Mometasone furoate had temporary relief of adenoid hypertrophy-related symptoms (84.6%) in comparison to the control group and placebo group during the duration of treatment. After cessation of treatment with local steroids, all cases experienced symptoms caused by adenoid hypertrophy, and by the end of the third month of follow up all cases underwent adenoidectomy. Conclusion: Mometasone furoate can temporarily reduce the adenoid size, reducing symptoms related to adenoid hypertrophy.

Dietary phytoestrogen diosgenin interrupts metabolism, physiology, and reproduction of Swiss albino mice: Possible mode of action as an emerging environmental contaminant, endocrine disruptor and reproductive toxicant.

Dietary phytoestrogens are the main source of environmental contamination due to their estrogen-mimicking and endocrine-disrupting effects, posing a threat to microbial, soil, plant, and animal health. Diosgenin, a phytosteroid saponin, is used in many traditional medicines, nutraceuticals, dietary supplements, contraceptives, and hormone replacement therapies against numerous diseases and disorders. It is important to be aware of the potential risks associated with diosgenin, as well as its potential to cause reproductive and endocrine toxicity. Due to the lack of research on the safety and probable adverse side effects of diosgenin, this work evaluated the endocrine-disrupting and reproductive toxicity of diosgenin in albino mice by following acute toxicity (OECD-423), repeated dose 90-day oral toxicity (OECD-468), and F1 extended one-generation reproductive toxicity (OECD-443) studies. Diosgenin was found to be slightly toxic, with LD50 for male and female mice being 546.26 and 538.72 mg/kg, respectively. Chronic exposure of diosgenin (10, 50, 100, and 200 mg/kg) generated oxidative stress, depleted antioxidant enzymes, disturbed homeostasis of the reproductive hormones, and interrupted steroidogenesis, germ cell apoptosis, gametogenesis, sperm quality, estrous cycle, and reproductive performance in the F0 and F1 offspring. Long-term oral exposure of diosgenin to the mice disturbed the endocrine and reproductive functions and generated transgenerational reproductive toxic effects in F0 and F1 offspring. These results suggest that diosgenin should be used carefully in food products and medical applications due to its potential endocrine-disrupting and reproductive toxic effects. The findings of this study provide a better understanding of the potential adverse effects of diosgenin and the need for appropriate risk assessment and management of its use.

5-Fluorouracil-Loaded PLGA Nanoparticles: Formulation, Physicochemical Characterisation, and In VitroAnti-Cancer Activity.

The major goal of this investigation was to prepare a drug delivery of polymeric nanoparticles (NPs) from 5-fluorouracil (FU) that could be delivered intravenously and improve the therapeutic index of the FU. In order to achieve this, interfacial deposition method was used to prepare FU entrapped poly-(lactic-co-glycolic acid) nanoparticles (FU-PLGA-NPs). The influence of various experimental settings on the effectiveness of FU integration into the NPs was assessed. Our findings show that the technique used to prepare the organic phase and the ratio of the organic phase to the aqueous phase had the greatest impact on the effectiveness of FU integration into NPs. The results show that the preparation process produced spherical, homogenous, negatively charged particles with a nanometric size of 200 nm that are acceptable for intravenous delivery. A quick initial release over 24 h and then slow and steady release of FU from the formed NPs, exhibiting a biphasic pattern. Through the human small cell lung cancer cell line (NCI-H69), the in vitro anti-cancer potential of the FU-PLGA-NPs was evaluated. It was then associated to the in vitro anti-cancer potential of the marketed formulation Fluracil®. Investigations were also conducted into Cremophor-EL (Cre-EL) potential activity on live cells. The viability of NCI-H69 cells was drastically reduced when they were exposed to 50 µg·mL-1 Fluracil®. Our findings show that the integration of FU in NPs significantly increases the drug cytotoxic effect in comparison to Fluracil®, with this potential effect being particularly important for extended incubation durations.

Design, Physical Characterizations, and Biocompatibility of Cationic Solid Lipid Nanoparticles in HCT-116 and 16-HBE Cells: A Preliminary Study.

In this study, pEGFP-LUC was used as a model plasmid and three distinct cationic lipids (dioleyloxy-propyl-trimethylammonium chloride [DOTMA], dioleoyl trimethylammonium propane [DOTAP], and cetylpyridinium chloride [CPC]) were tested along with PEG 5000, as a nonionic surfactant, to prepare glyceryl monostearate (GMS)-based cationic solid lipid nanoparticles (cSLNs). Both the type and quantity of surfactant had an impact on the physicochemical characteristics of the cSLNs. Thermal analysis of the greater part of the endothermic peaks of the cSLNs revealed they were noticeably different from the individual pure compounds based on their zeta potential (ZP ranging from +17 to +56 mV) and particle size (PS ranging from 185 to 244 nm). The addition of cationic surfactants was required to produce nanoparticles (NPs) with a positive surface charge. This suggested that the surfactants and extensive entanglement of the lipid matrix GMS provided support for the behavioral diversity of the cSLNs and their capacity to interface with the plasmid DNA. Additionally, hemolytic assays were used to show that the cSLNs were biocompatible with the human colon cancer HCT-116 and human bronchial epithelial 16-HBE cell lines. The DOTMA 6-based cSLN was selected as the lead cSLN for further ex vivo and in vivo investigations. Taken together, these new findings might provide some guidance in selecting surfactants to prepare extremely efficient and non-toxic cSLN-based therapeutic delivery systems (e.g., gene therapy).

Long-term consumption of fermented pork fat-based diets differing in calorie, fat content, and fatty acid levels mediates oxidative stress, inflammation, redox imbalance, germ cell apoptosis, disruption of steroidogenesis, and testicular dysfunction in Wistar rats.

There is a dearth of experimental evidence available as to whether the consumption of fermented pork fat (FPF) food has any harmful effects on metabolism and reproduction due to its excessive calories, high fat content, and fatty acid methyl ester (FAME) levels. We hypothesized that exposure to a FPF-diet with excessive calories, a high fat content, and high FAME levels alters testicular physiology and metabolism, leading to permanent damage to the testicular system and its function. Thirteen-week-old male rats (n = 20) were assigned to a high-calorie, high-fat diet (FPF-H, fat-60%, 23 kJ/g), a moderate-calorie, moderate-fat diet (FPF-M, fat-30%, 17.5 kJ/g), a low-calorie and low-fat diet (FPF-L, fat-15%, 14.21 kJ/g) compared to the standard diet (Control, fat-11%, 12.56 kJ/g) orally for 90 days. GC-MS analysis of the three FPF-diets showed high quantities of saturated fatty acids (SFAs) and polyunsaturated fatty acids-ω6 (PUFA-ω6) and low levels of monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids-ω3 (PUFA-ω3) compared to the control diet. Consequently, the levels of serum FAMEs of the FPF-diet fed rats were significantly increased. In addition, a high level of n-6:n-3 PUFA towards PUFA-ω6 was observed in the serum of FPF-diet fed rats due to the high content of linoleic, γ-linolenic, and arachidonic acid. Long-term consumption of FPF-diets disturbed the anthropometrical, nutritional, physiological, and metabolic profiles. Furthermore, administration of FPF-diets generated metabolic syndrome (dyslipidemia, leptinemia, insulin resistance, obesity, hepato-renal disorder and function), increased the cardiovascular risk factors, and triggered serum and testis inflammatory markers (interleukin-1↑, interleukin-6↑, interleukin-10↓, leukotriene B4↑, prostaglandin↑, nitric oxide↑, myeloperoxidase↑, lactate dehydrogenase↑, and tumor necrosis factor-α↑). Activated testis oxidative stress (conjugated dienes↑, lipid hydroperoxides↑, malondialdehyde↑, protein carbonyl↑, and fragmented DNA↑) and depleted antioxidant reserve (catalase↓, superoxide dismutase↓, glutathione S-transferase↓, reduced glutathione↓, glutathione disulfide↑, and GSH:GSSG ratio↓) were observed in FPF-diet fed rats. Disrupted testis histoarchitecture, progressive deterioration of spermatogenesis, poor sperm quality and functional indices, significant alterations in the reproductive hormones (serum and testis testosterone↓, serum estradiol↑, serum luteinizing hormone↓, and follicle-stimulating hormone↑), were noted in rats fed with FPF diets than in the control diet. Severe steroidogenic impairment (steroidogenic acute regulatory protein, StAR↓; 3ß-hydroxysteroid dehydrogenase, 3ß-HSD↓; and luteinizing hormone receptor, LHR↓), deficiency in germ cells proliferation (proliferating cell nuclear antigen, PCNA↓), and abnormally enhanced testicular germ cell apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling, TUNEL assay↑; B-cell lymphoma-2, BCL-2↓; Bcl-2-associated X protein, BAX↑; and BAX/BCL-2 ratio↑) were remarked in the FPF-diet administered rats in comparison with the control diet. In conclusion, the long-term feeding of an FPF-diet with excessive calories, a high fat content, and high FAME levels induced oxidative stress, inflammation, and apoptosis, resulting in metabolic syndrome and hampering male reproductive system and functions. Therefore, the adoption of FPF diets correlates with irreversible changes in testis metabolism, steroidogenesis, germ cell proliferation, and apoptosis, which are related to permanent damage to the testicular system and function later in life.

Functional bioinspired nanocomposites for anticancer activity with generation of reactive oxygen species.

Cancer is a debilitating and deadly disease caused by the uncontrolled growth of aberrant cell populations. This disease cannot always be controlled with traditional therapies and medicines. Different medicines are being used for this purpose, however these medicines have their side effects and are harmful to healthy cells. A better way to cure cancer disease is by limiting the agglomeration of cancer cells, minimizing their growth and their population by destroying these harmful cells. This could be achieved by controlling the function of mitochondria and DNA in cancer cells with the use of biocompatible materials with tuneable physical properties. Accordingly, research is ongoing as to the use of nanomaterials and nanotechnology in medicine. Zinc oxide semiconductor nanoparticles have displayed good anticancer behaviour. They have unique properties such as biocompatibility, good stability, and are environmentally friendly. Owing to these characteristics, they are focused on biological applications such as drug delivery and cancer therapy. In the present research work, zinc oxide, titanium dioxide nanoparticles and titanium oxide-zinc oxide nanocomposites were successfully trailed for anti-cancer activity. Pure zinc oxide nanoparticles (ZnO NPs), titanium dioxide nanoparticles (TiO2 NPs) and their nanocomposites (TiO2+ZnO NPs) were prepared by the co-precipitation technique. The structural properties were investigated by X-ray diffraction, which confirmed the Wurtzite structure of pure ZnO NPs. The morphology of the NPs was checked by scanning electron microscopy. For incident light having a higher energy band gap of nanomaterials, the electrons are excited to the conduction band and these electrons generate reactive oxygen species (ROS). The efficacy of these nanomaterials was checked by exposing the NPs to the human liver cancer cell HepG2. The MTT assay describes anticancer activity via cell viability. The cell viability of composites was observed to be greater than pure ZnO NPs. Their results showed that the structure of ZnO NPs remains the same with composites of TiO2 NPs, but the band gap of the composite was intermediate for individual samples. It also showed that the anticancer activity of composites was also less than pure ZnO NPs which is due to the reduction of ROS generation. This is observed that nanocomposites of ZnO and TiO2 could be effective in the development of a treatment of human liver cancer cells.

Determination of pioglitazone hydrochloride by flow injection chemiluminescence tris(2,2'-bipyridyl)ruthenium(II)-silver(III) complex system.

A novel flow injection-chemiluminescence (FI-CL) approach is proposed for the assay of pioglitazone hydrochloride (PG-HCl) based on its enhancing influence on the tris(2,2'-bipyridyl)ruthenium(II)-silver(III) complex (Ru(bipy)3 2+ -DPA) CL system in sulfuric acid medium. The possible CL reaction mechanism is discussed with CL and ultraviolet (UV) spectra. The optimum experimental conditions were found as: Ru(bipy)3 2+ , 5.0 × 10-5  M; sulfuric acid, 1.0 × 10-3  M; diperiodatoargentate(III) (DPA), 1.0 × 10-4  M; potassium hydroxide, 1.0 × 10-3  M; flow rate 4.0 ml min-1 for each flow stream and sample loop volume, 180 µl. The CL intensity of PG-HCl was linear in the range of 1.0 × 10-3 to 5.0 mg L-1 (R2 = 0.9998, n = 10) with limit of detection [LOD, signal-to-noise ratio (S/N) = 3] of 2.2 × 10-4  mg L-1 , limit of quantification (LOQ, S/N = 10) of 6.7 × 10-4  mg L-1 , relative standard deviation (RSD) of 1.0 to 3.3% and sampling rate of 106 h-1 . The methodology was satisfactorily used to quantify PG-HCl in pharmaceutical tablets with recoveries ranging from 93.17 to 102.77 and RSD from 1.9 to 2.8%.

Ameliorative effects of supranutritional selenium on TLR-4-NF-kB-TNF-α-mediated hepatic oxidative injury and inflammation in goats fed high concentrate diet.

We examined whether surplus dietary selenium (Se) supply could alleviate high concentrate (HC) diet-induced hepatic oxidative stress (OS) and inflammation. Eighteen young goats were distributed into three groups; were fed low (LC, concentrate: forage; 35: 65), high concentrate (HC, 65: 35), or Se-supplemented HC (HCSe, 65: 35 + 0.5 mg Se kg-1 diet) diets for 10 weeks. Short chain fatty acids, OS markers and immunoinflammatory genes expressions were assessed through gas chromatograph, kits, and RT-qPCR, respectively. Compared with LC, HC diet increased (p < .05) colonic and serum lipopolysaccharide (LPS) levels and induced hepatic oxidative injury by increasing (p < .05) malondialdehyde (MDA) levels and decreasing (p < .05) activities of glutathione peroxidase, superoxide dismutase, and catalase. HC diet altered hepatic mRNA expressions of toll-like receptor-4 (TLR-4), cluster of differentiation-14 (CD-14), tumor necrosis factor-α (TNF-α), TNF receptor-associated factor-6 (TRAF-6), nuclear factor kappa B (NF-κB), interleukin-1ß (IL-1ß), IL-10, IL-13, LPS-binding protein (LBP), serum amyloid A (SAA), α-acid glycoprotein (AGP), and albumin (ALB). Conversely, extra-Se supply lowered LPS and attenuated antioxidant status and inflammation in liver. In conclusion, HC diet induced oxidative lesions and TLR-4 pathway-mediated inflammation, whereas supranutritional Se alleviated oxidative and inflammatory lesions through TLR-4 pathway regulation in goat liver.

Dosimetric impact of tumor position displacements between photon and proton stereotactic body radiation therapy for lung cancer.

Purpose: To investigate the impact of tumor position displacements (TPDs) on tumor dose coverage in photon and proton stereotactic body radiation therapy (SBRT) treatments for lung cancer patients. Methods: From our institutional database of 2877 fractions from 770 lung cancer patients treated with photon SBRT in 2017-2021, 163 fractions from 88 patients with recorded iso-center shifts of >1.5 cm in any direction under kV-cone-beam CT guidance were identified. By double registrations with bony and tumor alignments, the difference between the iso-center shifts of these two alignments was categorized as TPDs. One fraction from each of 15 patients who had TPD magnitudes >3 mm were selected for this study. For each patient, one proton plan using intensity modulated proton therapy (IMPT) with robust optimization was generated retrospectively. All photon plans had V100%RX>99% of GTVs and V100%RX>98% of ITVs. Proton plans were evaluated with two worse-case scenario (voxelwise worst and worst scenario) using 5mm and 3.5% uncertainty to achieve the same planning goals as the corresponding photon plans. These two evaluation proton plans were named proton-1st and proton-2nd plans. The dosimetric effect of TPD was simulated by shifting tumor contours with the corresponding shift on patient specific planning CT and by recalculating the dose of the original plan. Results: The range of magnitude of TPDs was 3.58-28.71 mm. In photon plans, TPDs did not impact tumor dose coverage, still achieving V100%RX of the GTV≥99% and V100%RX of the ITV≥98%. In proton plans for patients with TPDs>10 mm, inadequate target dose coverage was observed. More specifically, 8 fractions of proton-1st plans and 4 fractions of proton-2nd had V100%RX of the GTV<99% and V100%RX of the ITV<98%. Conclusions: Adequate tumor dose coverage was achieved in photon SBRT for magnitude of TPDs up to 20 mm. TPDs had greater impact in proton SBRT and adaptive planning was needed when the magnitude of TPDs>10 mm to provide adequate tumor dose coverage.

Ethnic predisposition, risk factors and breast cancer presentation; a 10-year data. Single centered prospective cohort study from Karachi.

Background: Breast cancer, a leading cause of mortality among females, has been the center of research for many decades. Work is in progress to advance the research worldwide and in our region. This study is conducted to look into regional ethical predilection/age, clinical presentation/stage, pathological subtypes and risk factors of BC among patients of Karachi, with the aim of proposing a ground in our policy making regarding protocol setting for screening and management of BC patients. Methods: A prospective cohort study started at public Hospital, Karachi from 2010 to 2020.500 females with histo-pathologically proven BC selected. History, clinical examination, radiological and histo-pathological data retrieved; data regarding age, ethnicity, family history, parity, marriage/menopause, stage/lump size/symptoms were filled on pro-forma. Primary outcomes were age, ethnicity, family history, stage/histological type and menopausal status of our cohort while secondary outcomes were parity, marriage, symptoms and lump size/site. Data analyzed using SPSS in ranges and percentages. Results: Among different ethnicities, Makrani were the most affected(34%). Majority were premenopausal females ≤50yrs (78%). Infiltrating ductal carcinoma (88.8%) was the commonest subtype. Family history was positive in few (5.8%). Parity and marital status had no effect on our population. Breast lump (88%) was the commonest presenting symptom and 51% of our patients had the right side involved. Upper outer quadrant (51%) was the most involved quadrant and the majority (46%) were stage II. Conclusions: Age of presentation is around a decade earlier in our region, with women of Makrani descent more prone to develop BC. 2/3rd of patients were premenopausal, with lump breast as primary complaint. Majority of patients presented in stage-II. Results of age and racial predilection in our population suggest us to concentrate future research more on genetic profiling so we incorporate the results to devise population specific protocols with reference to age, presentation, BC type, ethnicity & risk factors.Record submitted retrospectively at ClinicalTrials.govt on 09-07-2022 NCT05458570 .

Asymmetric impacts of disaggregated energy consumption and oil price fluctuations on the MENA net oil-exporting and importing economies.

This paper asymmetrically analyzes the impact of energy consumption and oil price fluctuations on the economic growth of the MENA net oil-exporting and importing nations from 1990 to 2019 using panel nonlinear autoregressive distributed lag (PNARDL) model developed by (Salisu and Isah, Econ Model 66:258-271, 2017). The findings revealed that for the net-oil exporting countries, the impact of nonrenewable energy on economic growth is nonlinear in both terms, where in the both terms, high consumption of nonrenewable energy is influencing economic growth and its low consumption is limiting it. Furthermore, the impact of renewable energy is linear and it is influencing and limiting economic growth in both terms respectively. Moreover, the impact of oil price fluctuations on economic growth is linear in the long run and nonlinear in the short run, where in the long run, increase in it is not influencing economic growth but in the short run, while its decrease has no effect. For the net-oil importing countries, the impact of nonrenewable energy on economic growth is nonlinear in both terms, where in the long run, high consumption of nonrenewable energy is influencing economic growth but in the short run, it is discouraging it; however, in both terms, low consumption of nonrenewable energy has no effect. In addition, in the long run, the impact of renewable energy is nonlinear but linear in the short run; however, none of its impacts is significant in both terms. Also, the impact of oil price fluctuations on economic growth is linear in both terms and in the both terms, it is influencing economic growth. Nonetheless, for all the variables, the impacts are higher in the net-oil exporting countries. Policy recommendations were provided.

Frequency of osteoarthritis and functional outcome of operated tibial plateau fractures: A minimum of 5 years follow up.

OBJECTIVE: Tibial plateau is an important weight bearing surface and its fractures are the result of axial compressive forces. Post-traumatic osteoarthritis (PTOA) occurs despite anatomical joint reconstruction. In this study we determined the incidence of PTOA after primary management of tibial plateau fractures and determined the risk factors of PTOA of patients whose results were published at 24 months and now we present a five year follow up of the same patients. METHODS: In this study, we presented the prospective data of 109 patients who were managed for tibial plateau fractures, from August 2009 to June 2018 a Jinnah postgraduate medical centre. Data of patients regarding clinical and radiological, functional outcome (according to the American Knee Society criteria), post-procedural visual analogue scale (VAS) pain score was included. Incidence of development of PTOA was noted in each patient using the Ahlbäck classification. RESULTS: Out of 109 patients with tibial plateau fractures, 81 (74.3%) were male and 28 (25.7%) were female. Mean time lag from injury to surgery was 10.14±9.07 days. Overall incidence of osteoarthritis was 50 (45.9%). Advanced age >50 years (odds ratio 9.1 (3.7-22.1), p-value <0.0001), female gender (odds ratio; 3.40 (1.36-8.46), p-value 0.007), VAS score >4 ((odds ratio; 73.28 (15.7-341.5), p-value <0.001)), Articular depression (odds ratio; 35.25 (11.49-108.1), p-value <0.001) and degree of mal-alignment (odds ratio; 25.72 (9.30-71.12), p-value <0.001) were found to be the risk factors of PTOA. While excellent functional outcomes were protective for PTOA (odds ratio; 4.8, p-value <0.001). Thirty out of fifty patients (60%) suffering from secondary arthritis of the knee required knee replacement (TKR). Twenty-one patients (70%) were males that underwent TKR. CONCLUSIONS: There is a high proportion of osteoarthritis following tibial plateau fixation. The risk factors that related to the development of secondary arthritis our cohorts were increased age, male gender, a decrease in AKSS and a higher VAS group. Knee arthroplasty is the only option for our cohorts with severe posttraumatic arthritis.

Osetosynthesis of Fractures neck femur with cannulated screws: Evaluation of risk factors for post-operative complications.

OBJECTIVE: To evaluate the risk factors for postoperative complications in fracture neck femur treated with cannulated screws. METHODS: This cross sectional series was performed at the Department of Trauma and Orthopaedics, Jinnah Postgraduate Medical Centre, Karachi from January 2015 to December 2019. A Total of 149 patients with close fracture neck femur of either gender between 20-60 years of age were included in the study. Patients with hip arthritis and pathological fractures such as tumours were excluded. Minimum three cannulated screws were used to fix the fracture with parallel configuration in compression mode. Patients were followed and evaluated for fracture healing and related complications such as nonunion and Avascular necrosis for two years. Descriptive statistics were calculated and stratification was done. Post stratification chi square test was applied taking p-value ? ≤0.05 as statistically significant. RESULTS: There were 113 (75.8%) male and 36 (24.2%)female patients. Mean age was 37.54±10.66 years. Mean operation time was 38.56±4.61 minutes. Out of these, 93 (62.4%) injuries were caused by motor vehicle accident, 34(22.8%) fall and 22(14.8%) by sports injury. Garden type III fracture was observed in 69 (46.3%) patients followed by 41 (27.5%) fractures of grade-IV. Fracture union was observed in 126 (84.6%) patients at a mean time of 4.0±1.1months and non-union in 23 (15.4%) cases whereas rate of avascular necrosis was noted in 28 (18.8%) cases and were significantly associated with age, injury mode, time from injury to surgery and fracture classification. Non-union was significantly associated with open reduction and delayed fixation of fracture for more than 24 hours. CONCLUSIONS: Although cannulated screws are a universally accepted method of fixation for femoral neck fractures, the incidence of complications such as Avascular necrosis and non-union is quite high particularly in young males meeting a motor vehicle accident, undergoing open reduction for displaced fractures even with early diagnosis and treatment.

Can mini PCNL achieve the same results as RIRS? The initial single center experience.

BACKGROUND: Urolithiasis is a prevalent disease worldwide with high recurrence rate, minimally invasive interventions have largely replaced open ones, namely PCNL and RIRS. Miniaturization, optical improvements, and modern laser types made these procedures safe and effective in the management of single renal stones.Aim of the study: Is to compare the effectiveness of mini PCNL with RIRS in the treatment of single renal stone of ≤25 mm. PATIENTS AND METHODS: This prospective study that included 60 patients with single renal stones of ≤25 mm and were treated by either mini PCNL (group A) or RIRS (group B). The study was performed during the period from October 2020 to April 2021. RESULTS: The mean operative time RIRS group was 43.6 ± 10.493, while for miniPCNL it was 36.6 ± 7.035 (P = 0.004). The stone free rate in RIRS and miniPCNL group was 70% and 90% respectively (P = 0.053). The need for JJ stent was higher in RIRS compared to miniPCNL group (70% vs. 40%) respectively (P = 0.02). The duration of hospital stay in miniPCNL was 38.2 h compared to 16.7 h for RIRS group (p = 0.0001). The rate of postoperative hemoglobin drop was higher in MiniPCNL compared to RIRS (P = 0.0001). There was no significant difference regarding complication rates between both groups. CONCLUSION: Mini-PCNL FOR the treatment of renal stones sized ≤25 mm has high stone free rate, shorter operative time, less requirement for JJ stent and near similar post-operative pain and complications compared to RIRS.

Venlafaxine demonstrated anti-arthritic activity possibly through down regulation of TNF-α, IL-6, IL-1ß, and COX-2.

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used to treat depression. Previous studies demonstrated its anti-nociceptive and anti-inflammatory activities through the suppression of pro-inflammatory cytokines. Present research aimed to explore its anti-arthritic potential. Different in-vitro assays including egg albumin, bovine serum albumin denaturation and human red blood cell (RBC) membrane stabilization assays along with in-vivo models of formaldehyde and complete Freund's adjuvant-induced arthritis were used to study its anti-arthritic effect. Venlafaxine inhibited egg albumin and bovine serum albumin denaturation and preserve the integrity of red blood cells membrane in concentration-dependent manner. In formaldehyde-induced arthritis venlafaxine significantly (p < 0.001) reduced the paw edema on treatment for 10 days. Chronic administration of venlafaxine for 28 days in Freund's adjuvant-induced arthritis model decreased the paw volume (p < 0.001), arthritic index (p < 0.01), flexion pain score (p < 0.05), mobility score (p < 0.05), and improved the stance score (p < 0.05). Venlafaxine also significantly declined the rheumatoid factor (p < 0.01) and C-reactive protein (p < 0.05) levels and increased the RBC count (p < 0.01) and Hb value (p < 0.001). Upon PCR analysis venlafaxine remarkably turndown the mRNA expression of TNF-α, IL-6, IL-1ß, and COX-2. Taken together it is inferred from current findings that venlafaxine possesses the significant anti-arthritic activity and could be a potential therapeutic option for the treatment of rheumatoid arthritis.