Targeting SRD5A1 and MMP-2/NLRP3/TGF-ß1 axis alleviates the amlodipine-induced gingival hyperplasia in rats: Emerging role of saw palmetto and folic acid.

Saw palmetto (SAW), the herbal drug used to treat prostatic hyperplasia, exerts its antiproliferative effects by blocking steroid 5 alpha-reductase (SRD5A1) activity, that has also been involved in gingival hyperplasia (GH) pathogenesis. Concurrently, folic acid (FA) could reduce GH prevalence via its antioxidant and anti-inflammatory effects. Thus, this study tended to assess the potential therapeutic efficacy of SAW, alone and along with FA, against amlodipine-induced gingival inflammation and overgrowth in rats. Rats were grouped into (CONT, AIGH, SAW, SAW-treated, FA-treated, and SAW + FA-treated). SAW and FA were administered once daily for 4 weeks. Gingival SRD5A1, CTGF, GSK-3ß, and NLRP3 expressions, as well as T, DHT, MDA, TAC, ET-1, and MMP2 levels were determined. In addition, histopathological and immunohistochemical analyses of TNF-α, IL-6, TGF-ß1, and α-SMA were documented. Results declared that SAW and FA administration markedly ameliorated amlodipine-associated GH and may be presenting a novel therapeutic avenue in the future.

Triple injection peri-sartorius (TIPS) block for postoperative analgesia after total knee arthroplasty: Randomised controlled study.

Background and Aims: Motor-sparing analgesia after total knee arthroplasty (TKA) is crucial. The primary endpoint was the postoperative visual analogue scale (VAS) score after triple injection peri-sartorius (TIPS) block after TKA. Secondary endpoints were postoperative morphine consumption, 24-h postoperative ambulation distances and the degrees of active knee extension. Methods: After general anaesthesia or spinal anaesthesia administration and before surgical incision, 80 patients undergoing TKA were randomised into group TIPS (received ultrasound-guided TIPS block where 40 ml 0.25% bupivacaine and 4 mg dexamethasone were injected: 10 ml at the distal femoral triangle, 10 ml above the sartorius and 20 ml at the distal adductor canal) and group FNB (femoral nerve block; received ultrasound-guided FNB with 20 ml 0.25% bupivacaine mixed with 4 mg dexamethasone). Postoperative pain score was noted and compared. Results: Dynamic VAS scores were lower in the TIPS group than in FNB, while the resting VAS scores were not significantly different. Mean (standard deviation [SD]) postoperative morphine consumption was 5.82 (2.47) mg in the TIPS group (95% confidence interval [CI] 5.03,6.61) versus 9.87 (2.99) mg in the FNB group (95% CI 8.91,10.83). Ambulation distances and active postoperative knee extension in the TIPS group showed greater significance than in the FNB group (TIPS: 18.0 [7.37] m, 95% CI 15.64,20.35] vs. FNB: 8.95 [5.93] m, 95% CI 7.05,10.84) and (TIPS: 52.12 [16.39], 95% CI 46.88,57.33 vs. FNB: 26.05 [11.10], 95% CI 22.501,29.59). Nausea was more evident in FNB patients. Conclusion: TIPS block provides superior analgesia than FNB with motor sparing of the quadriceps after TKA.

Single puncture combined lumbar erector spinae plane and quadratus lumborum block (SEQ block) in acetabular fracture surgeries: randomized clinical trial.

BACKGROUND: Acetabular fracture surgery can cause severe postoperative pain. A combined lumbar erector spinae plane block and paraspinous sagittal shift quadratus lumborum block may augment analgesia. METHODS: Fifty two patients undergoing posterior column acetabular surgery were divided into: Group Single puncture combined lumbar Erector spinae and Quadratus lumborum block (SEQ), patients who received SEQ block before anesthesia; and Group morphine (MOR), those who received general anesthesia (GA) and morphine. RESULTS: Demographic characteristics were comparable. The heart rate and mean arterial blood pressure were significantly lower in the SEQ group than in the MOR group between 60 and 180 min intraoperatively (P < 0.001). Postoperative resting and dynamic visual analogue scale scores in the SEQ group were significantly lower than those in the MOR group at all studied periods (P = 0.022-0.001), except at 20 and 24 h postoperatively. Fentanyl was required in all MOR group patients at a mean dose of 110.0 ± 28.42 µg while 18 patients required fentanyl in SEQ group at a mean dose of 60.55 ± 25.54 µg. Postoperative morphine consumption was significantly less in SEQ group (6.33 ± 2.37 mg) than MOR group (17.0 ± 2.55 mg). Postoperative nausea and vomiting were recorded in eight and four patients in MOR and SEQ group, respectively. No complications associated with the block technique were observed. CONCLUSIONS: The SEQ block reduces the postoperative opioid consumption and provides stable intra and postoperative hemodynamics without observed complications in posterior column acetabular surgery.

First confirmed case of multisystem inflammatory syndrome in adult in Egypt.

Key Clinical Message: Our case report demonstrates extremely uncommon data associated with MIS-A, such as cholestatic jaundice, anemia, and quickly progressing pneumonia. IVIG and pulse steroid medications are the best treatments for improving clinical outcomes. Abstract: We report a case of multiple organ dysfunctions due to MIS-A in an adult with a history of suspected COVID-19. Our case demonstrates extremely uncommon data associated with MIS-A, such as cholestatic jaundice, anemia, and quickly progressing pneumonia. IVIG and pulse steroid medications are the best treatments for improving clinical outcomes.

Hand Injuries During COVID-19 UK Lockdown: How Did the Pandemic Affect 1-Year Functional Outcomes?

BACKGROUND: The COVID-19 outbreak was declared a pandemic in March 2020, forcing the United Kingdom into a national lockdown. The aim was to evaluate the effect of this lockdown on hand injuries referred through the trauma and orthopedics virtual fracture clinic (VFC) service and their subsequent management given limited resources. This study also aimed to identify complications and evaluate functional outcomes. METHODS: Patients referred through VFC at Queen Alexandra Hospital during April and May 2020 with hand injuries were analyzed. Isolated injuries to the carpus and wrist were excluded. Controls were compared over identical time spans prior to lockdown and after the restrictions were eased. Functional outcomes were measured using the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, at 12 months after injury. RESULTS: There was a 68% reduction in referrals of hand injuries during lockdown. Lower numbers of sporting injuries were seen, in contrast to an increased rate of falls, crush injuries, and recreational cycling. Despite a higher number of patients being discharged from VFC during lockdown, there were no increased rates of complications from conservatively managed hand fractures. Eighty percent reported low QuickDASH scores with a median of 2.3. Satisfaction was high, with 73% either satisfied or very satisfied with their treatment and outcome. CONCLUSION: This study demonstrates that there remains a burden of hand trauma during lockdowns, and therefore, service provision for future lockdowns should consider this. Most patients can be managed conservatively, and a high proportion can be discharged from VFC with low complication rates and high satisfaction.

Comparison Between Ultrasound-guided Caudal Analgesia versus Peripheral Nerve Blocks for Lower Limb Surgeries in Pediatrics: A Randomized Controlled Prospective Study.

Background and Aim: Ultrasound (US) guided regional analgesia is a safe and effective method in providing perioperative analgesia in pediatrics with a high success rate rapid onset and fewer side effects. The aim of this study was to compare the efficacy of US-guided caudal block versus US-guided peripheral nerve blocks (femoral and sciatic nerve blocks) in providing perioperative analgesia in pediatrics undergoing unilateral lower limb surgery. Methods: Children aged 1-12 years scheduled for unilateral lower limb surgery during the period from January 2020 to December 2021 were randomly allocated into two groups. Group C where pediatrics received US-guided caudal block, while in group P, pediatrics received US-guided femoral and sciatic nerve blocks after the induction of general anesthesia (GA). The primary aim was to compare the postoperative pain (evaluated by the COMFORT pain score) between the two groups. Secondary aims were to compare perioperative opioids used parents' satisfaction and occurrence of side effects. Results: Pediatrics who underwent unilateral lower limb surgeries were allocated into two groups (group C and group P). There was no significant difference between patients' baseline characteristics and the postoperative pain score at 2, 4, 16, and 20 h.' However there was a statistical significance at 6, 8, 12, and 24 h postoperatively, frequency of analgesia as well as the total postoperative dose of opiates (nalbuphine). Time to first analgesic (nalbuphine) requirement was significantly less in group C with a mean of (9.6±2.9 h) than in group P with a mean of (15.1±3.5 h). Parents of children in group P were more satisfied than those in group C with no recorded complications for both techniques. Conclusion: US-guided lower limb peripheral nerve block is a simple and safe method to provide adequate and more prolonged analgesia compared to US-guided caudal block for lower limb surgeries in pediatrics.

Efficacy of Sofosbuvir plus Ledipasvir in Egyptian patients with COVID-19 compared to standard treatment: a randomized controlled trial.

COVID-19 is a pandemic disease caused by SARS-CoV-2, which is an RNA virus similar to the hepatitis C virus (HCV) in the replication process. Sofosbuvir/ledipasvir is an approved drug to treat HCV infection. This study investigates the efficacy of Sofosbuvir/ledipasvir as a treatment for patients with moderate COVID-19 infection. This is a single-blinded parallel-randomized controlled trial. The participants were randomized equally into the intervention group that received Sofosbuvir/ledipasvir (S.L. group), and the control group received Oseltamivir, Hydroxychloroquine, and Azithromycin (OCH group). The primary outcomes were the cure rate over time and the incidence of serious adverse events. The secondary outcomes included the laboratory findings. 250 patients were divided equally into each group. Both groups were similar regarding gender, but age was higher in the S.L. group (p=0.001). In the S.L. group, 89 (71.2%) patients were cured, while only 51 (40.8%) patients were cured in the OCH group. The cure rate was significantly higher in the S.L. group (RR=1.75, p<0.001). Kaplan-Meir plot showed a considerably higher cure over time in the S.L. group (Log-rank test, p=0.032). There were no deaths in the S.L. group, but there were six deaths (4.8%) in the OCH group (RR=0.08, p=0.013). Seven patients (5.6%) in the S.L. group and six patients (4.8%) in the OCH group were admitted to the intensive care unit (ICU) (RR=1.17, P=0.776). There were no significant differences between treatment groups regarding total leukocyte and neutrophils count, lymph, and urea. Sofosbuvir/ledipasvir is suggestive of being effective in treating patients with moderate COVID-19 infection. Further studies are needed to compare Sofosbuvir/ledipasvir with new treatment protocols.

Piceatannol promotes hepatic and renal AMPK/SIRT1/PGC-1α mitochondrial pathway in rats exposed to reserpine or gamma-radiation.

Human exposure to radio-therapeutic doses of gamma rays can produce late effects, which negatively affect cancer patients' quality of life, work prospects, and general health. This study was performed to explore the role of Piceatannol (PIC) in the process of "mitochondrial biogenesis" signaling pathway as possible management of disturbances induced in stressed animal model(s) either by gamma-irradiation (IR) or administration of reserpine (RES); as a mitochondrial complex-I inhibitor. PIC (10 mg/kg BW/day; orally) were given to rats for 7 days, after exposure to an acute dose of γ-radiation (6 Gy), or after a single reserpine injection (1 g/kg BW; sc). Compared to reserpine or γ-radiation, PIC has attenuated hepatic and renal mitochondrial oxidative stress denoted by the significant reduction in the content of lipid peroxides and NO with significant induction of SOD, CAT, GSH-PX, and GR activities. PIC has also significantly alleviated the increase of the inflammatory markers, TNF-α and IL-6 and apoptotic markers, cytochrome c, and caspase-3. The decrease of oxidative stress, inflammation, and apoptotic responses were linked to a significant amelioration in mitochondrial biogenesis demonstrated by the increased expression and proteins' tissue contents of SIRT1/p38-AMPK, PGC-1α signaling pathway. The results are substantiated by the significant amelioration in mitochondrial function verified by the higher levels of ATP content, and complex I activity, besides the improvement of hepatic and renal functions. Additionally, histopathological examinations of hepatic and renal tissues showed that PIC has modulated tissue architecture after reserpine or gamma-radiation-induced tissue damage. Piceatannol improves mitochondrial functions by regulating the oxidant/antioxidant disequilibrium, the inflammatory and apoptotic responses, suggesting its possible use as adjuvant therapy in radio-therapeutic protocols to attenuate hepatic and renal injuries.

Efficacy of Sofosbuvir plus Ledipasvir in Egyptian patients with COVID-19 compared to standard treatment: Randomized controlled trial

BackgroundCOVID-19 is a pandemic disease caused by SARS-CoV-2, which is an RNA virus similar to HCV in the replication process. Sofosbuvir/ledipasvir is an approved drug by the FDA to treat HCV infection. This study investigates the efficacy of Sofosbuvir/ledipasvir as a treatment for patients with moderate COVID-19 infection.. MethodsThis is a single-blinded parallel-randomized controlled trial. The participants were randomized equally into the intervention group received Sofosbuvir/ledipasvir (S.L. group), and the control group received Oseltamivir, Hydroxychloroquine, and Azithromycin (OCH group). The primary outcomes were the cure rate over time and the incidence of serious adverse events. The secondary outcomes included the laboratory findings. ResultsTwo hundred and fifty patients were divided equally into each group. Both groups were similar regarding gender, but age was higher in the S.L. group (p=0.001). In the S.L. group, 89 (71.2%) patients were cured, while only 51 (40.8%) patients were cured in the OCH group. The cure rate was significantly higher in the S.L. group (RR=1.75, p<0.001). Kaplan-Meir plot showed a considerably higher cure over time in the S.L. group (Log-rank test, p=0.032). There were no deaths in the S.L. group, but there were six deaths (4.8%) in the OCH group (RR=0.08, p=0.013). Seven patients (5.6%) in the S.L. group and six patients (4.8%) in the OCH group were admitted to ICU (RR=1.17, P=0.776). There was no significant difference between treatment groups regarding Total Leukocyte Count, Neutrophils count, Lymph and Urea. ConclusionSofosbuvir/ledipasvir is suggestive of being effective in treating patients with moderate COVID-19 infection. Further studies are needed to compare Sofosbuvir/ledipasvir with the new treatment protocols.

Fascio-Adipo-Cutaneous Lateral Advancement Flap for Treatment of Pilonidal Sinus: A Modification of the Karydakis Operation-Cohort Study.

BACKGROUND: Pilonidal sinus is a common chronic disease affecting young adults. Many surgical procedures have been developed for its treatment, but an optimal one has still not been achieved. This study presents a modification to the Karydakis operation. METHODS: A total of 265 patients with chronic pilonidal sinus between May 2008 and May 2015 were included in this study and submitted to fascio-adipo-cutaneous lateral advancement flap as 1-day case surgery. Any Septic complication was treated firstly. Follow-up examinations were conducted during the first three postoperative months at the outpatient clinic at regular intervals and thereafter by phone calls or direct examination to check for recurrences. RESULTS: Males constituted 93.6% with a mean age of 21.6 ± 7.7 year. The median disease duration was 15 months. Twenty-eight patients had recurrent disease. The mean operative time was 41.4 ± 12.7 min. The mean time out of work was 11.6 ± 4.6 days. Complications occurred in 19 patients (7.1%) in the form of seroma in six patients (2.2%), superficial wound infection occurred in nine patients (3.3%), cuticular wound disruption occurred in four patients (1.5%). All patients completed 3-months follow-up, but 48 patients were lost at variable intervals with the remaining 217 patients completed follow-up throughout the period of the study with a median follow-up of 43 months. No reported recurrence and 96.7% of the patients were satisfied about their wound. CONCLUSION: This modification is simple with low complication rate, no recurrence, and excellent patient satisfaction.

Gastric antral vascular ectasia in systemic sclerosis: Where do we stand?

Gastric antral vascular ectasia (GAVE) continues to be a challenge in both diagnosis and treatment. GAVE has a diverse group of associations and presumed causes, including cirrhosis, chronic renal failure and autoimmune connective tissue diseases. However, in most occasions, the management plan of GAVE itself is the same whatever the underlying disease by using Argon plasma coagulation (APC). Herein, we will discuss three cases of systemic sclerosis-associated GAVE presenting with either acute or chronic gastrointestinal bleeding showing variable responses to APC. Anemia and telangiectasia may be the first striking presentation of systemic sclerosis (SSc). Renal artery stenosis, aortic stenosis, widespread cutaneous and mucosal telangiectasia and hypertension seem to be associated with poor prognosis and should prompt rapid intervention and careful follow-up. Moreover, the hunt for molecular underpinnings of the broad array of vascular lesions in SSc has to include von Willebrand factor and endoglin. Eventually, we will review the recent alternatives that can be effective in SSc-GAVE, such as band ligation, hematopoietic stem cells transplantation and immunotherapy.

Comparative assessment of gastric emptying in obese patients before and after laparoscopic sleeve gastrectomy using radionuclide scintigraphy.

Radionuclide scintigraphy provides a standard physiologic evaluation of gastric emptying (GE) after laparoscopic sleeve gastrectomy (LSG). This operation can be associated with motor gastric dysfunction and abnormal GE. The aim of this study was to evaluate the short-term effect of LSG on GE quantitative indices for liquids and solids compared with preoperative results. Forty obese patients were divided into two equal groups, the liquid and solid groups. Tc-sulfur colloid GE scintigraphy was performed on all patients submitted to LSG before and after surgery (1-4 weeks for liquids and 4-6 weeks for solids). The quantitative indices included half emptying time (T1/2) and percentage gastric retention at 15, 30, and 60 min for liquids and at 30, 60, 90, and 120 min for solids. A modified technique was used to label a boiled egg in order to be tolerated by the patients. T1/2 was significantly enhanced after LSG compared with baseline (25.3±4.4 vs. 11.8±3.0 min for liquids and 74.9±7.1 vs. 28.4±8.3 min for solids, respectively, P<0.001). The percentage of gastric retention in operated patients was significantly less than that at baseline for liquids at 15, 30, and 60 min (33.9±5.6, 17.7±3.9, and 7.5±2.8% vs. 69.4±10.5, 55.6±14.95, and 26.1±4.7%, respectively, P<0.001), as well as for solids at 30, 60, 90, and 120 min (42.0±11.1, 20.8±6.1, 11.0±5.9, and 3.8±2.7% vs. 79.9±8.7, 67.4±12.2, 37.0±10.9%, and 13.8±4.4%, respectively, P<0.001). The significant acceleration of GE of liquids and solids after LSG may have contributed to weight loss in the immediate postoperative period (4-6 weeks). It remains to be determined whether the weight loss will continue beyond that period.

Probiotic prophylaxis after pullthrough for Hirschsprung disease to reduce incidence of enterocolitis: a prospective, randomized, double-blind, placebo-controlled, multicenter trial.

OBJECTIVE: Hirschsprung-associated enterocolitis (HAEC) is one of the most troublesome problems encountered after a pullthrough. We hypothesized that prophylactic administration of probiotics after a pullthrough procedure would decrease the incidence of HAEC. STUDY DESIGN: A prospective, double-blind, placebo-controlled, randomized trial was conducted at 2 children's hospitals. Infants undergoing pullthrough were randomized to probiotic or placebo for a period of 3 months post-pullthrough. Primary outcome was incidence of post-operative HAEC. Other outcomes included severity of HAEC by clinical grade, number of HAEC episodes and extent of aganglionosis. Pearson Chi Square analysis, as well as logistic regression, was used for statistical analysis. RESULTS: Sixty-two patients were recruited (Sites: A=40; B=22). One was lost to follow up and one immediate post-op death was not included in final analysis. Probiotics were administered to 32 patients. Distribution of placebo/probiotics was equal between sites (P=0.858). Mean age at pullthrough was 6.5 ± 8.1(± SD) months. The incidence of HAEC was 28.3%. The incidence of HAEC was not statistically different between probiotic and placebo study groups. CONCLUSIONS: Incidence of HAEC was not reduced with prophylactic probiotics. Future studies are needed to better determine the etiology and possible ways of preventing this complex condition.

Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients.

BACKGROUND: Colorectal cancer is a common cancer all over the world. Aberrations in the cell cycle checkpoints have been shown to be of prognostic significance in colorectal cancer. METHODS: The expression of cyclin D1, cyclin A, histone H3 and Ki-67 was examined in 60 colorectal cancer cases for co-regulation and impact on overall survival using immunohistochemistry, southern blot and in situ hybridization techniques. Immunoreactivity was evaluated semi quantitatively by determining the staining index of the studied proteins. RESULTS: There was a significant correlation between cyclin D1 gene amplification and protein overexpression (concordance = 63.6%) and between Ki-67 and the other studied proteins. The staining index for Ki-67, cyclin A and D1 was higher in large, poorly differentiated tumors. The staining index of cyclin D1 was significantly higher in cases with deeply invasive tumors and nodal metastasis. Overexpression of cyclin A and D1 and amplification of cyclin D1 were associated with reduced overall survival. Multivariate analysis shows that cyclin D1 and A are two independent prognostic factors in colorectal cancer patients. CONCLUSIONS: Loss of cell cycle checkpoints control is common in colorectal cancer. Cyclin A and D1 are superior independent indicators of poor prognosis in colorectal cancer patients. Therefore, they may help in predicting the clinical outcome of those patients on an individual basis and could be considered important therapeutic targets.