Tyrosine kinase inhibitors (TKIs) have been studied extensively in cancer research, ultimately resulting in the approval of many drugs for cancer therapy. Recent evidence from reported clinical cases and experimental studies have suggested that some of these drugs have a potential role in diabetes treatment. These TKIs include imatinib, sunitinib, dasatinib, erlotinib, nilotinib, neratinib, and ibrutinib. As a result of promising findings, imatinib has been used in a phase II clinical trial. In this review, studies that used TKIs in the treatment of both types of diabetes are critically discussed. In addition, the different molecular mechanisms of action of these drugs in diabetes models are also highlighted to understand their antidiabetic mode of action.

Background: Practices of Do-Not-Resuscitate (DNR) orders show discrepancies worldwide, but there are only few such studies from Saudi Arabia. Objective: To describe the practice of DNR orders in a Saudi Arabian tertiary care ICU. Methods: This retrospective study included all patients who died with a DNR order at the ICU of King Saud Medical City, Riyadh, Saudi Arabia, between January 1 to December 31, 2021. The percentage of early DNR (i.e., ≤48 hours of ICU admission) and late DNR (>48 hours) orders were determined and the variables between the two groups were compared. The determinants of late DNR were also investigated. Results: A total of 723 cases met the inclusion criteria, representing 14.9% of all ICU discharges and 63% of all ICU deaths during the study period. The late DNR group comprised the majority of the cases (78.3%), and included significantly more patients with acute respiratory distress syndrome (ARDS), community acquired pneumonia (CAP), acute kidney injury, and COVID-19, and significantly fewer cases of readmissions and malignancies. Septic shock lowered the odds of a late DNR (OR = 0.4, 95% CI: 0.2–0.9; P = 0.02), while ARDS (OR = 3.3, 95% CI: 2–5.4; P < 0.001), ischemic stroke (OR = 2.5, 95% CI: 1.1–5.4; P = 0.02), and CAP (OR = 2, 95% CI: 1.3–3.1; P = 0.003) increased the odds of a late DNR. Conclusion: There was a higher frequency of late DNR orders in our study compared to those reported in several studies worldwide. Cases with potential for a favorable outcome were more likely to have a late DNR order, while those with expected poorer outcomes were more likely to have an early DNR order. The discrepancies highlight the need for clearer guidelines to achieve consistency.

Background: Atrophic edentulous mandible is a challenging clinical condition. Studies assessing the use of ultrashort implants to support overdentures are scarce; the optimum photobiomodulation (PBM) dose for enhancing osseointegration is yet unknown. Objective: This study aimed to evaluate and compare mandibular overdentures assisted by two versus four ultrashort implants with adjunctive PBM therapy using two doses. Materials and Methods: A total of 36 implants were placed in 12 edentulous male participants and they were randomly allocated to Group I (mandibular overdentures assisted by two ultrashort implants) or Group II (by four ultrashort implants). Fully guided implant placement was performed, and then a split-mouth design was implemented. The participants received PBM by diode laser (660 nm). Dose A (3.75 J/cm²) and Dose B (7.5 J/cm²) were applied to the right and left implant (s), respectively. Implant stability, peri-implant probing depth (PIPD), and modified gingival index (MGI) were evaluated at baseline, and at 6 and 12 months after loading. Results: After 12 months, the implant stability values were significantly higher in Group II compared with Group I (P < 0.001). A significant difference was observed in between the PIPDs of both groups (Group I: 2.35 ± 0.54 mm; Group II: 1.69 ± 0.35 mm; P = 0.001). The mean MGI values were low for both groups (Group I: 0.75 ± 0.58; Group II: 0.51 ± 0.41). Conclusions: Mandibular overdentures supported by four ultrashort implants had a more favorable clinical outcome, while PBM doses A and B were comparable in all evaluated parameters. Trial Registration: ClinicalTrials.gov Identifier: NCT03540316.

Background: Deoxynivalenol (DON) is a trichothecene mycotoxin with demonstrated cytotoxicity in several cell lines and animals, primarily owing to inflammation and reactive oxygen species accumulation. Ruscogenin (RGN), a steroidal sapogenin of Radix Ophiopogon japonicus, has significant anti-thrombotic/anti-inflammatory effects. Objective: The aim of this study was to assess the protective role of RGN against DON-induced oxidative stress, which occurs through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and is regulated by phosphoinositide 3-kinases/protein kinase B (PI3K/AKT). Methods: The effects were examined using the HepG2 cell line. RGN and DON were suspended in serum-free medium. Cells were seeded onto plates, and then RGN, DON, or both were added over 24 h in triplicates for each group. Results: RGN conferred protection against DON-exhibited cytotoxicity against HepG2 cells. RGN pretreatment downregulated the expression of DON-induced TNF-α and COX-2 and the formation of reactive oxygen species in a dose-dependent manner. RGN upregulated the expression of Nrf2 and its antioxidant proteins as well as mRNA levels of HO-1/NQO-1/HO-1/Nrf2. Similarly, treatment with DON + RGN resulted in upregulation of the pI3K/pAKT signaling pathway in a dose-dependent manner. Finally, RGN was also found to inhibit the DON-induced apoptosis by upregulating the levels of cleaved proteins and downregulating the expression of Bcl2. Conclusion: The study demonstrates that RGN suppresses hepatic cell injury induced by oxidative stress through Nrf2 via activation of the pI3K/AKT signaling pathway.

Background: Burn injury is associated with a high mortality risk. Recent epidemiological data on burn injury and mortality rate from Saudi Arabia is lacking. Objective: This study aimed to analyze the survival rates and its predictability using the Baux score in patients with burn injury at a tertiary care hospital in Saudi Arabia. Materials and Methods: This retrospective study included all patients admitted to the burn unit at King Fahd Hospital of the University, Al Khobar, between March 2014 and February 2020. Patients' burn characteristics and calculated revised Baux scores were collected. The age, burn wound size, type of burn, burn extension, and Baux score of the survivors and non-survivors were compared. Results: A total number of 102 patients were included, and their mean age was 24.2 years (range: 9 months to 78 years). The mean affected total body surface area was 26.4%. Ninety patients (88%) suffered from flame/scald burn. The mortality rate was 17.6% (18 patients); all these patients had flame burns. No patient with a revised Baux score ≥110 survived (n = 14; 77% of the total deaths), while there was no mortality at score <36. Inhalational injuries were reported in 18 patients, of which 13 (72%) died. Patients with patent airway and no inhalation injury were 19 times more likely to survive than those with a compromised airway (P < 0.001). In terms of the depth of burn, partial thickness increased the likeliness of survival by 10 times compared with full thickness (P < 0.003). Conclusion: Inhalational injury and burn size were the most prognostic factors of burn injury in this study. As all cases of mortality were from flame burns, regulation on flammable materials and safety measures should be promoted to the public.

Background: Acute kidney injury (AKI) is associated with an increase in patient mortality and high rates of renal/non-renal complications. Late detection of the disease has been associated with worse prognosis, but no such study has been conducted from Saudi Arabia. Objectives: To assess the impact of early nephrology referral on the outcomes of patients with AKI. Methods: This retrospective record review included all adult patients (≥18 years) with AKI who were referred to the Nephrology Department at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, between May 2019 and July 2020. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. AKI patients evaluated by nephrologists were stratified into early referral group (i.e., referral in <48 h from the first detection of AKI) and late referral group (referral ≥48 h after the first detection of AKI). Results: A total of 400 patients met the inclusion criteria, of which 264 (66%) were early referrals. A significant association was found between delayed referral and mortality rates and length of hospital stay (for both, P = 0.001). Late referral was also significantly associated with increased likeliness of the need for renal replacement therapy (P = 0.037) and sepsis (P = 0.005). Conclusions: The outcomes were worse for patients with AKI receiving late referrals to nephrologists. Raising the awareness of AKI among non-nephrologists would likely increase the proportion of earlier referrals.

Background: Evidence-based practice (EBP) has gained significant importance in clinical practice worldwide, including physiotherapy, but there are limited studies that have assessed the knowledge, attitude, and behaviors of Saudi physiotherapists toward EBP. Objective: To determine the beliefs, attitudes, knowledge, and experience of Saudi physiotherapists in public hospitals of the Eastern Province of Saudi Arabia toward EBP as well as identify barriers that limit the integration of EBP in clinical practice. Materials and Methods: This cross-sectional design included all Saudi physiotherapists working in four major tertiary hospitals in the Eastern Province of Saudi Arabia. The Evidence-Based Practice Questionnaire was used to elicit responses. The association between attitudes, awareness, and knowledge scores and the demographic data such as age group, years of experience, and level of education was assessed. Results: The questionnaire was distributed to a total of 171 physiotherapists, of which 118 (69%) responded. About 90% of the participants agreed or strongly agreed that EBP is necessary for clinical practice. However, about 25%, 19%, and 18% of the participants reported that EBP does not consider clinical limitations, support physiotherapy intervention, or consider patients' physiotherapy preferences, respectively. The most common barrier in the implementation of EBP in daily clinical practice was insufficient time (>50%), followed by self-efficacy in retrieving evidence from the literature and translating research findings into clinical practice. Years of experience, age, and gender were significant factors associated with physiotherapists' beliefs and attitudes toward implementing EBP. Conclusions: Although EBP was favored, several barriers exist that hinder its adoption by physiotherapists. Institutional support and research skill development may help accelerate EBP adoption levels and should be considered by policymakers.

Background: Understanding the health-seeking behaviors help in increasing the effectiveness and efficiency of the health-care system; however, there is lack of knowledge regarding the health-seeking behavior of the elderly population in the Kingdom of Bahrain. Objective: The objective of this study was to identify the morbidity profile and determine the health-seeking behavior of the elderly population. Methods: This cross-sectional study included all elderly patients (≥60 years) who attended four primary health-care centers that represent four governorates with the largest catchment area in the Kingdom of Bahrain between June 19 and August 31, 2021. Information concerning their sociodemographic data, morbidity profile and health-seeking behavior were collected through direct interviewing using a structured, predesigned and pretested questionnaire. Results: A total of 414 elderly patients were included, with the majority being Bahraini (89.1%) and male (55%). The most prevalent morbidity was hypertension (67.6%), followed by hyperlipidemia (54.7%), diabetes (52.6%), and arthritis (32.1%); arthritis was significantly more common among females than males (P < 0.001). The majority reported the reason for their visit being “repeat prescription” (32.1%). Almost one-third (28.2%) attempted self-management prior to their visit, and almost half (46.7%) reported seeking non-professional medical advice. The majority rated their health as good (39.4%) and moderate (38.2%). Less than one-third (28%) reported having had a health problem for which they did not attend to a health care facility. Conclusion: The study highlighted the morbidity profile and the health-seeking behavior among elderly population in Bahrain, which may serve as a point from which further efforts may be directed to improve the services.

Background: Knowledge regarding surgical site infections (SSIs) can help reduce hospital stay, morbidity, and mortality associated with SSI. Objectives: This study aimed to determine the knowledge and awareness of SSI among patients undergoing surgeries across Saudi Arabia. Methods: This multi-center cross-sectional study included adult patients (aged >18 years) who underwent surgery at six centers located across the five regions of Saudi Arabia. A 36-item questionnaire was used to elicit data regarding demographics, patient's health status, procedures, and hospitalization history and awareness and knowledge about SSIs. Results: A total of 375 patients were included (equally for all five regions of Saudi Arabia). Most patients were male (55.7%) and aged 18–34 years (44%). Most respondents (49.1%) had poor awareness; being illiterate and from the Northern region were significant factors (P = 0.001). Patients with no history of surgery (P = 0.001) or SSI (P = 0.003) also had poor awareness levels. In terms of knowledge, 45.8% and 35.2% of the participants had fair and poor knowledge, respectively, with the level of knowledge being significantly associated with region (P = 0.001). Patients those aged >65 years had poor knowledge (P = 0.033), while of males had good knowledge (P = 0.02). Patients with no history of surgery had poor knowledge of SSIs (P = 0.003). Only 32.8% of the patients recalled having been educated by healthcare workers. About 42% learned of SSIs from sources outside the hospital, with internet/social media platforms accounting for 48.4% of such sources. Conclusion: A significant proportion of the patients included in this study had poor awareness and knowledge of SSIs. The study highlights the need for strengthening the preoperative patient education in Saudi Arabia to reduce the likeliness of SSIs.

Background: Medical schools in Saudi Arabia generally do not integrate ultrasound training in undergraduate medical study despite its widespread use. Objective: To determine the efficiency of a short course in acquiring basic ultrasound skills at the undergraduate medical level. Subjects and Methods: Fourth-year medical students of Jazan University (2016/2017; N = 118) were divided into 13 groups. A radiology expert provided each group with a 50-min lecture on “ultrasound in clinical practice” and a 2-h hands-on ultrasound training session. Then, the students were invited to participate in the study by completing a questionnaire eliciting data regarding their opinion, experiences, and satisfaction level for the session and then undertaking skill assessment using two OSCE stations. Results: Eighty-one students (68.6%) were enrolled in the study (male: 42; female: 39). The mean scores were high for handling the probe (4.33 ± 1.01) and identifying kidney (4.46 ± 1.08) and liver (4.22 ± 0.97), and moderate for identifying spleen (3.89 ± 0.75), aorta (3.35 ± 0.44), and hepatorenal pouch (3.05 ± 0.35). The students were highly satisfied with the course (4.37 ± 1.01). In the first OSCE station that assessed ultrasound techniques, the mean score was 14.96 (of 18 points; 83.11%) for males and 15.40 (85.56%) for females. In the second station that used static ultrasound image with common pathology, the mean score was 2.4 (of 2.5 points) for both males and females. Conclusion: Undergraduate medical students in this study gained adequate skills and satisfaction in terms of using ultrasound and identifying anatomy following the short course. This study highlights the benefits of introducing programs dedicated to ultrasound for undergraduate medical students in Saudi Arabia.

Background: Osteoporosis is characterized by a decrease in bone mineral density, thereby increasing the risk of pathological fractures. It is a common complication of chronic kidney disease. However, there is limited local data on the prevalence of osteoporosis in end-stage renal disease. Objective: The current study evaluated the epidemiology of osteoporosis in end-stage rental disease patients at a Saudi Arabian tertiary care center. Methods: This cross-sectional retrospective study was conducted using data obtained between 1 January 2016 and 31 December 2019 at the Dialysis Center at King Abdulaziz Medical City, Riyadh, Saudi Arabia. End-stage rental disease patients who were aged ≥50 years and underwent hemodialysis for at least 1 year were included, while those with documented metabolic bone disease and absence of bone mineral density data were excluded. Results: Sixty-four end-stage rental disease patients undergoing hemodialysis met the inclusion criteria. The patients underwent bone mineral density measurement at the discretion of the treating physician. The mean patients' age was 73 ± 11.5 years and 76% were women. The overall prevalence of osteoporosis was 37.5%, and it was similarly distributed among women and men (38.8% and 33.3%, respectively). Nine of the 15 male patients (60%) and 24 of the 49 female patients (49%) had fractures. Twenty-five (39%) patients used glucocorticoids. Osteoporosis was most commonly identified in the femoral neck (26.2%), followed by proximal femur (19.4%), and lumbar spine (18.8%). A high rate of osteoporosis was significantly associated with older age and being underweight. Conclusion: A high rate of low bone mineral density was demonstrated in end-stage renal disease patients. The femoral neck was the most common osteoporosis site in this patient population, and advanced age and underweight were possible risk factors for low bone mass.

Background: Neck and low back pain are very common worldwide. Hanna somatic education (HSE) is a method of neuromuscular (mind–body) movement retraining that helps in managing pain, but its efficacy has not yet been studied. Objective: To evaluate the clinical effect of HSE on low back and neck pain and determine differences in pain, use of pain medication, and number of doctor visits before and after 6 months of HSE sessions. Methodology: This retrospective study included patients with neck and/or low back pain of >2-month duration who underwent HSE sessions between January 2016 and January 2018 and completed a minimum one follow-up session. Two to five one-to-one sessions of 40–60 min once every 1–2 weeks for 2–8 weeks were provided for each patient. Pain levels were recorded at each visit using the Wong-Baker FACES Pain Rating Scale. Data regarding medication use and number of doctor visits for pain management were also recorded. Results: A total of 103 patients were included, of which 81 (78.6%) were female. Completing a mean 2.8 HSE sessions resulted in a significant pain level reduction. There were significant reductions in the mean low back, neck, and low back + neck pain values between the first and the last visits (P < 0.001). In the 6 months before and after the HSE intervention, the number of patients using pain medication decreased from 53 (53.5%) to 14 (13.6%), respectively, and the mean number of doctor visits reduced significantly from 2 (±1.6) to 0.5 (±1.16) (P < 0.001), respectively. Conclusion: Clinical sessions of HSE were found to significantly reduce chronic spinal pain. Further investigations are recommended regarding evidence-based treatment of HSE in patients with muscles pain.

Sjogren's syndrome (SS) is a chronic autoimmune disease that is characterized by focal lymphocytic infiltration of the exocrine glands. SS mostly affects middle-aged women, and results in an increased risk of developing malignant neoplasm, particularly hematologic malignancies. The concurrent occurrence of SS, ovarian cancer, and autoimmune disease is very rare. Here, we present a case with postoperative digital autoamputation in a young Sjogren's patient diagnosed with high-grade serous ovarian cancer. The patient was later also diagnosed with antiphospholipid syndrome. Clinicians should note that female genital tract malignancies might occur in autoimmune diseases. In addition, when planning for surgery, they should also be aware of the possibility of another autoimmune disease and different patterns of postoperative complications such as venous thromboembolism and thrombophlebitis. A multidisciplinary approach is required to achieve successful management. To the best of the authors' knowledge, this is the second case with concurrent SS and ovarian cancer and the first case with concurrent SS, antiphospholipid syndrome, and ovarian cancer.

Appendiceal mucocele is an appendicular dilatation secondary to the intraluminal accumulation of mucous material. Adequate pre-operative diagnosis and surgical resection remains the standard management. Here, we present three cases of appendiceal mucocele. In the first case, a 60-year-old female presented with signs and symptoms of acute appendicitis and was admitted and operated. An inflamed distended globular cystic mass of appendix measuring 10 × 6 × 4 cm with a wide base was found and the patient underwent right hemicolectomy. In the second case, a 30-year-old male with symptoms and signs of acute appendicitis was admitted to the emergency department. An open surgery was performed and a distended, tense, and inflamed appendix without perforation of size 6 × 1 × 1 cm was discovered and removed. The diagnosis of mucocele appendix was suspected and confirmed by postoperative dissection of the specimen and histopathology. In the third case, a 25-year-old female patient was subjected to diagnostic laparoscopy in view of non-specific pain abdomen. A diagnosis of mucocele of appendix was made intraoperatively and removed using a specimen bag. Appendiceal mucocele with acute presentation is a rare pathology that clinically resembles acute appendicitis. Preoperative detailed investigations to reach a definitive diagnosis are critical for adequate surgical resection and overall outcome.