Design of Experimental Approach for Development of Rapid High Performance Liquid Chromatographic Process for Simultaneous Estimation of Metoprolol, Telmisartan, and Amlodipine from Formulation: Greenness and Whiteness Evaluation.

The design of an experimental approach, the Box-Behnken design, was implemented to optimize the chromatographic condition to develop a rapid HPLC procedure for quantification of a ternary mixture of metoprolol (MET), telmisartan (TEL), and amlodipine (AML) from the formulation. The perturbation plots, contour, and 3D response surface pictures were developed to study the impact of each variable on the analytes' retention time and the probable interaction between the parameters with fewer chromatographic runs. The optimized HPLC method separated the three analytes within 5 min with excellent selectivity and peak shape on a Zorbax C18 HPLC column using acetonitrile and phosphate buffer (20 mM, pH 5.8) with isocratic elution at a 1.1 mL/min flowrate. A wavelength 230 nm was utilized to monitor the elute. The validation of proposed method demonstrated a wide linearity range of 10-200 µg/mL for MET and TEL and 5-50 µg/mL for AML along with an excellent correlation coefficient. The correctness of the HPLC approach was further confirmed by excellent recovery of the added amount of analytes utilizing the standard addition technique. The recommended HPLC approach was employed safely for quality assurance of the formulation, because the evaluation of the method's greenness and whiteness confirmed the environmentally friendly nature of the approach.

Nanoscale plasmonic logic gates design by using an elliptical resonator.

This study implemented AND, NAND, OR, XOR, NOR, XNOR, and NOT plasmonic logic gates using the finite element method. The all-optical nanoscale logic gates were designed using a single structure based on the technology of insulator-metal-insulator nanoscale plasmonic waveguides. The phase of optical waves and the position of the control and input ports are the most important factors for attaining the optimal transmission value based on interference between the input and control ports. The transmission threshold is 35%, and 850 nm is the operating wavelength. This design creates nanoscale logic gates with a structure dimension of 250nm×250nm. The transmission threshold, modulation depth, contrast ratio, and insertion loss criteria were proposed to evaluate the efficacy of the all-optical gates.

Nanoscale plasmonic combinational logic circuits based on an elliptical resonator.

The half-adder (HA) and half-subtractor (HS) plasmonic combinational logic circuits are explained using a finite element method with a COMSOL software package. The combinational circuits are created using insulator-metal-insulator technology with nanoscale plasmonic structures. In order to achieve an excellent transmission value, the phase angle of optical waves and the position of the control and input ports are the more crucial elements. In this design, the nanoscale combinational circuits are realized at a 35% transmission threshold to distinguish between the logic "0" and logic "1" stand on the interference between the input and control ports with 540n m×250n m dimensions and an 850 nm resonant wavelength. The modulation depth, contrast ratio, and insertion loss have 97.38%, and 11.84 and 3.3 dB for the HA, and they have 92.38%, and 7.12 and -1.41d B for the HS, respectively.

Calcium Channel Blockers in Conjunction with Standard Iron-Chelating Agents for ß-Thalassemia Major: Systematic Literature Search.

Thalassemia is a genetic mutation of the α- or ß-globin chains that lead to defective erythropoiesis. This study aimed to collect evidences from all published studies that investigated the clinical effectiveness of calcium channel blockers (CCBs) in conjunction with chelation therapy for reducing iron overload in patients with thalassemia. A systematic search was conducted in PubMed, Institute for Scientific Information (ISI) Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Virtual Health Library. Original studies reporting the use of CCBs in patients with thalassemia were included for meta-analysis. A total of five randomized studies including 210 patients were included with a follow-up period of 3-12 months. There was no significant difference between amlodipine and control groups in increasing the heart T2* magnetic resonance imaging (MRI) [mean difference (MD) 95% confidence interval (95% CI) = -1.9 (-4.4 to 0.5), p = 0.119] or reducing the liver iron concentration [MD 95% CI = -0.046 (-0.325 to 0.2), p = 0.746]. Although there were no serious adverse events reported in the included trials, further studies are recommended to strengthen our findings.

Intraoral Inflammatory Leiomyosarcoma: A Case Report and Literature Review.

Inflammatory leiomyosarcoma (ILMS) is a rare malignant soft tissue neoplasm with smooth muscle differentiation, prominent inflammatory infiltration, and near-haploidization. It is extremely rare in the head and neck region, and no intraoral cases have been reported. The lesion was initially diagnosed as a malignant spindle cell neoplasm at the referring laboratory. Microscopic examination of blocks of excised fragmented lesion revealed a cellular neoplasm composed of plump, spindle-shaped cells with blunt-ended and elongated nuclei and eosinophilic fibrillary cytoplasm arranged in a fascicular, herringbone to haphazard pattern. The tumor cells were interspersed with mixed inflammatory infiltration and were diffusely positive to desmin, SMA, H Caldesmon, and MYOD1. The diagnosis came as Inflammatory leiomyosarcoma. This case is the first reported case of ILMS involving the oral cavity. Even though this lesion is very rare, this neoplasm should be included in the differential diagnosis of a spindle cell lesion with marked lymphohistiocytic infiltration.

An Extremely Rare and Aggressive Case of Undifferentiated Carcinoma With Osteoclast-Like Giant Cells of the Pancreas Presenting as a Paraneoplastic Syndrome: A Case Report and Literature Review.

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is a rare tumor type of pancreatic cancer. Paraneoplastic syndromes, an idiopathic inflammatory myositis characterized by various skin manifestations (such as dermatomyositis (DM)), cannot be attributed to the primary tumor itself. Here, we report an unusual case of UC-OGC presenting as a paraneoplastic syndrome, the first reported from Saudi Arabia and the Arabian Gulf states. A 49-year-old Eritrean woman with known DM was referred to our hospital with a left-sided pleural effusion. Computed tomography of the abdomen revealed a large necrotic splenic mass (~17 × 12.9 × 18.2 cm). The patient underwent exploratory laparotomy with en bloc resection of the mass (splenectomy, distal pancreatectomy, and partial excision of the left hemidiaphragm). Following a histopathological examination of the mass, UG-OGC of the pancreas, presenting as a paraneoplastic syndrome, was diagnosed. To our knowledge, this case is the first to present a paraneoplastic syndrome associated with UC-OGC. The identification of an exceedingly rare tumor presenting atypically as a paraneoplastic syndrome shows the importance of conducting comprehensive examinations of patients with malignancies, emphasizing the need for more reports of similar cases.

Appendiceal neoplasms in Saudi Arabia: prevalence and clinicopathological profile.

BACKGROUND: The appendix is a small organ with no particular known function. Primary appendiceal neoplasms (ANs) are rare. While the prevalence is increasing worldwide over the past two decades, no apparent increase in the prevalence of ANs has been reported in the Arabian Gulf States. Recently, a significant decline in the age at diagnosis of some types of ANs has been reported worldwide, with a female predominance. OBJECTIVES: Evaluate the prevalence and clinicopathological characteristics of ANs within our institution in Saudi Arabia and compare them to limited existing studies from different regions as well as the Arabian Gulf States. DESIGN: Retrospective cohort. SETTING: Tertiary care center in Riyadh. PATIENTS AND METHODS: All patients who underwent appendectomy and had the appendix submitted for histopathological evaluation between May 2015 and June 2020 were included to allow for a follow-up of 5 years or more at the time of data collection. MAIN OUTCOME MEASURES: Demographics, clinical presentations, surgical interventions, histopathological findings, complications, and recurrence rates. SAMPLE SIZE: 25 AN patients. RESULTS: Of 1110 patients, 25 had ANs (13 female and 12 male participants) with a mean (standard deviation) age of 54.6 (14.1) years. Only 40% presented with acute appendicitis, 64% had comorbidities, and less than 50% underwent laparoscopic appendectomy. Histopathologically, 72% were low-grade appendiceal mucinous neoplasms (LAMNs). Complications were minimal grades (Clavien-Dindo classification), with 80% experiencing none. The mean hospital stay was 9.96 days. Local recurrence occurred in 8% of cases, and distant metastasis was documented in one adenocarcinoma case. However, the 5-year overall and disease-free survival rates were 88% and 80%, respectively. CONCLUSIONS: The incidence of ANs is increasing in Saudi Arabia with the higher prevalence of LAMNs. The pathological examination of the resected appendix played a pivotal role in the diagnosis of ANs. LIMITATIONS: Data collected retrospectively, a single institution, and a small population.

A huge benign gastric schwannomas presented with upper and lower gastrointestinal bleeding: a case report and literature review.

Gastric schwannomas (GS) are rare mesenchymal tumors from Schwann cells in the gastrointestinal (GI) tract, representing 2-6% of such tumors. We report a 52-year-old woman who experienced abdominal pain, hematemesis, and melena, initially suspected of having a GI stromal tumor through ultrasound and computed tomography abdomen. Despite no active bleeding found during an upper endoscopy, she underwent a successful open subtotal gastrectomy, with histopathology confirming GS. The diagnosis of GS, which may mimic other GI conditions, relies heavily on imaging and histopathological analysis due to its nonspecific symptomatology, including the potential for both upper and lower GI bleeding. This case underscores the diagnostic challenges of GS and highlights surgical resection as the preferred treatment, generally leading to a favorable prognosis.

Clinicohistological Characteristics of Patients with Oral Lichenoid Mucositis: A Retrospective Study for Dental Hospital Records.

Oral lichenoid mucositis (OLM) of the oral mucosa is a histological diagnosis mainly characterised by a band of inflammatory infiltrate in lamina propria and basal cell degeneration. These features describe oral lichen planus or oral lichenoid reaction. However, it could be seen in oral dysplasia. The study aimed to assess the demographics and clinicohistological characteristics of patients with OLM and their relevance to dysplastic changes in the oral mucosa. This was a cross-sectional and retrospective study of archived and electronic records of individuals with histological confirmation of OLM at King Saud University Medical City, Saudi Arabia. The descriptive and correlation assessments were used to describe the demographics and clinicohistological characteristics and their associations, respectively [p < 0.05]. The analysis included 140 records of patients with histological confirmation of OLM with a mean age of 47 (±13), and 57% (n = 81) were females. Notably, 40% of patients had at least one medical condition, mainly diabetes mellitus, 74% were asymptomatic, and 52% had lesions in the buccal mucosa. Dysplasia was seen in 18 (12%) of the 140 reviewed records. Regarding the associations between study variables, dysplastic changes were associated with the male gender [p = 0.024] and were of no significance with increased age [p = 0.594]. Moreover, having oral symptoms was associated with older age [p < 0.001], medical history of diabetes [p = 0.0132] and hypertension [p < 0.001]. The present study findings could help indicate the individuals with histologically confirmed OLM who suffer the most from the clinical disease and have an increased risk of dysplastic changes. Therefore, symptomatic management and long-term follow-up can be planned accordingly.

Intraoral angiosarcoma with unusual clinical presentation: A case report.

Introduction: Angiosarcoma is a rare and highly aggressive soft tissue malignancy originating from vascular and lymphatic endothelial cells. Epithelioid angiosarcoma is the rarest subtype of angiosarcoma, characterized by the proliferation of large polygonal cells with an epithelioid feature. The occurrence of these tumors in the oral cavity is highly uncommon, and immunohistochemistry staining is essential to differentiate epithelioid angiosarcoma from mimicking lesions. Aim: To present a case of intraoral angiosarcoma with an unusual clinical presentation and behavior and to report, to the best of our knowledge, a first primary appendix epithelioid angiosarcoma with metastasis foci in the oral cavity. Objectives: To discuss the clinical, histological, and immunochemical features of an unusual case of intraoral angiosarcoma. Case report: A 53-year-old Saudi female with an uncommon clinical presentation of intraoral angiosarcoma. The patient reported the lesion being painless, slowly growing, and of a six-month duration. The microscopic examination and immunohistochemical evaluation showed epithelioid angiosarcoma. The tumor cells were positive to ERG, FLI 1, and CD31 (focal) and negative to CK HMW, CD45, S100, HMB 45, D2-4, and CD 34. Discussion: Due to the extremely rare occurrence and non-characteristic presentation of angiosarcoma in the oral cavity, many lesions maybe included in the differential diagnosis. Thus, making the diagnosis of intraoral angiosarcoma difficult.

Unusual Acute, Massive Lower Gastrointestinal Bleeding Secondary to a Proximal Jejunal Gastrointestinal Stromal Tumor: A Case Report.

The most common primary non-epithelial neoplasms of the gastrointestinal (GI) tract are gastrointestinal stromal tumors (GISTs). Ten percent (10%) of GISTs arise from the jejunum. Usually, patients complain of abdominal discomfort, but they may present with complications such as intestinal obstruction or bleeding. This report describes a 35-year-old male who presented with unusually massive, acute lower GI bleeding. After resuscitation and investigations (including a contrast-enhanced computed tomography of the abdomen and lower GI endoscopy), the patient underwent diagnostic laparoscopy and bowel resection of the affected section with anastomosis, and he had an eventful postoperative course. Studies suggest that GI bleeding in GIST occurs due to the ulceration and necrosis of the overlying mucosa caused by the pressure effect of the mass. Small-bowel GISTs are categorized based on their size. Many guidelines have advocated conservative management for small GISTs (<2 cm) that are in the jejunum. This patient has a rare case of a small jejunal GIST with a rare presentation of massive lower GI bleeding. A multidisciplinary approach is useful in managing such cases, and our case showed that laparoscopic intervention is a feasible option in a stable patient with massive lower GI bleeding.

An Overview of Developmental Dysplasia of the Hip and Its Management Timing and Approaches.

Developmental dysplasia of the hip (DDH), if uncorrected, can result in several chronic abnormalities, including chronic hip pain, degenerative arthritis, and gait abnormalities. The outcome of DDH generally depends on the age of presentation; a worse prognosis is linked to a higher age of presentation. Although treatment continues to be a challenge, recent advancements in the field have improved our understanding of the disease, which has resulted in advancements in DDH surveillance during infancy and the reduction of complications with early intervention. The databases used for this overview include Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library, MEDLINE, and EMBASE. These databases were used to search for ongoing trials related to the management and diagnosis of DDH.

Is Appendiceal Diverticulitis Mimicking Acute Appendicitis?

Appendicular diverticulitis (AD) is a rare entity characterized by the inflammation of the arising diverticulum of the appendix. It has been reported to carry a high risk of perioperative complications, such as bleeding and perforation. Furthermore, multiple articles have highlighted the importance of diagnosing AD early due to its strong association with malignancies. Limited published cases concerning AD in our country and globally are available in the literature. Hence, we present in this article a case series of five exciting cases of incidental findings of AD that were initially diagnosed as acute appendicitis based on clinical evaluation and imaging findings. In our series, we performed a retrograde evaluation of the computed tomography scans of all five cases that showed diverticula. In conclusion, histopathological evaluation remains the method of choice to reach the definitive diagnosis; however, it is essential to highlight the relevance of imaging in diagnosing AD preoperatively in the early stages to reduce morbidity and mortality.

Assessing the risk of a clinically significant infection from a Microneedle Array Patch (MAP) product.

Microneedle Array Patches (MAPs) are an emerging dosage form that creates transient micron-sized disruptions in the outermost physical skin barrier, the stratum corneum, to facilitate delivery of active pharmaceutical ingredients to the underlying tissue. Numerous MAP products are proposed and there is significant clinical potential in priority areas such as vaccination. However, since their inception scientists have hypothesized about the risk of a clinically significant MAP-induced infection. Safety data from two major Phase 3 clinical trials involving hundreds of participants, who in total received tens of thousands of MAP applications, does not identify any clinically significant infections. However, the incumbent data set is not extensive enough to make definitive generalizable conclusions. A comprehensive assessment of the infection risk is therefore advised for MAP products, and this should be informed by clinical and pre-clinical data, theoretical analysis and informed opinions. In this article, a group of key stakeholders identify some of the key product- and patient-specific factors that may contribute to the risk of infection from a MAP product and provide expert opinions in the context of guidance from regulatory authorities. Considerations that are particularly pertinent to the MAP dosage form include the specifications of the finished product (e.g. microbial specification), it's design features, the setting for administration, the skill of the administrator, the anatomical application site, the target population and the clinical context. These factors, and others discussed in this article, provide a platform for the development of MAP risk assessments and a stimulus for early and open dialogue between developers, regulatory authorities and other key stakeholders, to expedite and promote development of safe and effective MAP products.

A Rare Case of Pancreatic Adenocarcinoma With Incidental Synchronous Hepatic and Sigmoid Colonic Metastasis: A Case Report and Literature Review.

Metastasis of pancreatic adenocarcinoma to the colon is a very rare condition that might be underdiagnosed and underreported in the literature. We report a very rare case of incidental findings of sigmoid metastasis secondary to pancreatic adenocarcinoma in a 60-year-old Saudi male, who is a non-smoker with a normal medical and surgical history. The patient presented to a primary care clinic with abdominal bloating and vague on/off abdominal pain for almost 1 year as well as unintentional weight loss without lower gastrointestinal (GI) symptoms. After the case was discussed in the multidisciplinary tumor board, the patient was started on systematic palliative chemotherapy. However, after receiving the first cycle, he started to deteriorate rapidly and succumbed to secondary cardiopulmonary arrest. Cases of synchronous metastasis of pancreatic adenocarcinoma to the colon might not be well known or common. However, a high index of suspicion and individualizing the workup tools may need to be used.

Enabling Intelligent IoTs for Histopathology Image Analysis Using Convolutional Neural Networks.

Medical imaging is an essential data source that has been leveraged worldwide in healthcare systems. In pathology, histopathology images are used for cancer diagnosis, whereas these images are very complex and their analyses by pathologists require large amounts of time and effort. On the other hand, although convolutional neural networks (CNNs) have produced near-human results in image processing tasks, their processing time is becoming longer and they need higher computational power. In this paper, we implement a quantized ResNet model on two histopathology image datasets to optimize the inference power consumption. We analyze classification accuracy, energy estimation, and hardware utilization metrics to evaluate our method. First, the original RGB-colored images are utilized for the training phase, and then compression methods such as channel reduction and sparsity are applied. Our results show an accuracy increase of 6% from RGB on 32-bit (baseline) to the optimized representation of sparsity on RGB with a lower bit-width, i.e., <8:8>. For energy estimation on the used CNN model, we found that the energy used in RGB color mode with 32-bit is considerably higher than the other lower bit-width and compressed color modes. Moreover, we show that lower bit-width implementations yield higher resource utilization and a lower memory bottleneck ratio. This work is suitable for inference on energy-limited devices, which are increasingly being used in the Internet of Things (IoT) systems that facilitate healthcare systems.

A Rare Case and Presentation of Traumatic Penetrating Aortic Arch Injury: A Case Report and Literature Review.

A penetrating injury to the thoracic aorta is an extremely rare, life-threatening condition, with a high overall mortality rate. The incidence of a penetrating injury to the aortic arch is unknown because the majority of patients die before receiving adequate treatment due to excessive bleeding. Through a literature review, 23 cases of favorable outcomes were found. We report the first case from the Arab Gulf states. We present the extremely rare case of a 23-year-old male who presented to the emergency department with stable hemodynamics after being stabbed in the left supraclavicular region. The investigation revealed that he suffered from aortic arch transection and contrast extravasation. The patient was rushed to the operating room, where a primary repair was performed through a median sternotomy approach. The patient was discharged on the 14th postoperative day without complications. Penetrating chest trauma (aortic arch injury) is uncommon, and it is typically fatal at the scene or time of injury, even in patients who arrive at the emergency department alive or while undergoing surgery. CT aortography should be performed on patients with normal vital signs but abnormal clinical findings suggestive of a vascular injury. For injuries of types II to IV without concomitant injuries, immediate surgical repair is recommended. Aortic arch penetrating injuries continue to be extremely lethal. Emergency surgical repair remains the standard of care and is associated with high morbidity and mortality rates. However, managing such uncommon injuries remains a formidable challenge. We encourage additional studies.

Outcomes of Sinus Laser Therapy in Sacrococcygeal Pilonidal Sinus Disease: A Single-Center Experience.

Sacrococcygeal pilonidal sinus disease (SPND) is an acquired chronic disease with no precise etiopathogenesis. The morbidity associated with the disease necessitates the implementation of new techniques, such as sinus laser therapy (SiLaT), to improve disease management. However, surgical techniques as of now are preferred as the mainstay mode of treatment. A retrospective study was conducted to evaluate and report the healing outcome of the application of SiLaT on patients with SPND at a tertiary center. All patients who underwent SiLaT for primary or recurrent pilonidal sinus from February 2012 to December 2019 were included in the study and followed up for at least six months. Forty-one participants (37 males (90.2%) and four females (9.8%)) were included. Of the participants, 58.5% presented with chief complaints of painful swelling with mucopurulent discharge. Most of the participants were students (43.9%). SiLaT was the primary intervention for 82.9% of the participants. The mean duration of hospital stays, resumption of regular activity, and complete wound healing by secondary intention were 30±21.5 hours, 18.4±14.3 days, and 6.5±6.6 weeks, respectively. Around 95.1% of wounds healed without complications. The overall recurrence rate was 24.4%, while the recurrence rate with SiLaT being the primary intervention was 11.8%. Only three (7.32%) patients experienced wound infections as postoperative complications. The visual analog scale (VAS) score decreased postoperatively in the first and second weeks to 3.9±3.2 and 1.9±1.9, respectively, and 78.1% of the total patients showed satisfaction post-surgical interventions. The current study showed that the SiLaT technique is a feasible technology with promising results to evolve. Further studies are encouraged.

A Constitutional Mismatch Repair Deficiency Syndrome Presented With an Advanced Rectal Cancer in a Juvenile Female: A Case Report and Literature Review.

The constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and challenging condition with a poor prognosis. It results from biallelic mismatch repair gene mutations and leads to multiorgan cancers. Therefore, we report the first case of advanced juvenile rectal cancer related to CMMRD syndrome in the Gulf region. She is a 13-year-old female, born to non-consanguineous parents with a positive family history of malignancy, presented with an eight-month history of a retractable bulging anal mass associated with diarrhea mixed with blood and constitutional symptoms. She was cachectic with café au lait spots all over her body. Upon investigation, she was found to have invasive rectal adenocarcinoma. The case was started on neoadjuvant chemoradiotherapy in addition to genetic testing which showed a homozygous pathogenic variant in PMS2, indicating CMMRD syndrome. The patient underwent pre-operative post-neoadjuvant reassessment followed by laparoscopic total proctocolectomy with ileal J-pouch creation and ileoanal anastomosis with temporary diverting loop ileostomy which later on was reversed with no complications or recurrence. The family declined to continue the adjuvant therapy but accepted the surveillance programs and genetic testing. Unusual or late presentation secondary to a very rare syndrome like CMMRD is a major challenge to clinicians, hence a high index of suspicion and proper utilization of genetics programs might be the best available solutions.

Complete bilateral blindness associated with ruptured anterior communicating artery aneurysm: A literature review and illustrative case.

Background: Anterior communicating artery (AcomA) aneurysms are considered one of the most common intracranial aneurysms, contributing to approximately 40% of the subarachnoid hemorrhages related to aneurysmal rupture. Aneurysms of the anterior circulation are commonly present with visual defects varying in their nature according to the aneurysmal site. However, complete bilateral vision loss associated with AcomA aneurysms is a significantly rare finding. We are reporting a case of complete bilateral blindness in a patient with a ruptured AcomA aneurysm with a literature review. Methods: We conducted a PubMed Medline database search by the following combined formula of subjects' headings: (((Intracranial Aneurysm [MeSH Terms]) AND (AcomA Aneurysm [Title/Abstract])) AND [(Vision loss OR Blindness [Text Word])) AND (case reports [Filter]). Additional articles were searched through the reference lists of the included articles. Results: Our review yielded a total of five cases. All the present cases revealed unilateral blindness only, and their outcomes after treatment vary from recovery of vision to unchanged complete vision loss - none of the cases found in the literature presented with bilateral blindness. Conclusion: AcomA aneurysms can be associated with visual loss in some cases. However, usually, the defect is unilateral. Studies of the visual defects, including potential bilateral complete blindness associated with rupture inferiorly, directed AcomA aneurysm, should be highlighted.