The impact of a restricted pregabalin prescription policy on drug utilization: An observational multicenter study.

Background: The Saudi Food and Drug Authority (SFDA) classified pregabalin as a controlled substance in 2018; however, whether this policy change has affected pregabalin use is unclear. This study examined the trends in pregabalin prescriptions before and after the SFDA restriction. In addition, the co-prescription of controlled analgesics and the use of pregabalin for approved indications were also evaluated. Method: A cross-sectional study was conducted on outpatient pregabalin prescriptions from three healthcare centers in Saudi Arabia. Interrupted time series analysis was used to assess changes over time in pregabalin prescriptions and the number of patients receiving pregabalin. June 2016 to June 2017 was identified as the pre-restriction period, and July 2018 to July 2019 as the post-restriction period. Results: In this study, 77,760 pregabalin prescriptions were identified. There were 9,076 patients on pregabalin in the pre-restriction period with 16,875 prescriptions, compared with 7,123 patients and 19,484 prescriptions post-restriction. The total number of pregabalin users decreased by 21.5% post-restriction, and prescriptions increased by 15.5%. There was no significant change in the monthly trends in pregabalin prescriptions before and after the restriction. However, the of tramadol and acetaminophen/codeine prescriptions in patients who were using pregabalin increased in the post-restriction period by 21% and 16.1%, respectively. Conclusion: Pregabalin use was reduced after the SFDA-enforced prescription restriction was implemented. This was accompanied by increased narcotics use in the post-implementation phase.

Empiric vs screening-based use of isoniazid for tuberculosis prophylaxis: Safety and effectiveness in lung transplant recipients in Saudi Arabia.

BACKGROUND: Tuberculosis (TB) is a major complication following transplantation. The likelihood of TB may be increased in transplant patients living in TB-endemic areas such as Saudi Arabia. In areas where TB is less common, guidelines recommend isoniazid (INH) for TB prophylaxis depending on patient and donor screening results. However, in TB-endemic regions, studies have supported its use in all transplant patients regardless of TB screening results. This study aimed to compare the safety and effectiveness of administering INH prophylaxis therapy based on the TB screening results of lung transplant (LT) recipients. METHODS: We conducted a single-center retrospective cohort study on LT recipients. The outcomes were compared between patients who were administered screening-based prophylaxis (SBP) with INH based on their tuberculin skin tests (TSTs) or QuantiFERON results and those who were administered empirical prophylaxis (EP) with INH regardless of TB screening results. The primary endpoint was the incidence of TB infection, and the secondary endpoints were INH-induced hepatotoxicity and INH resistance. RESULTS: A total of 50 patients received SBP and 30 received EP. TB incidences were 8% and 0%, respectively (P = .0487). One of these patients had INH resistance, and one patient experienced INH-induced hepatotoxicity (P = .1591); both were in the SBP group. CONCLUSION: The low rates of TB infection, INH-induced hepatotoxicity, and INH resistance in the EP group suggest that INH prophylaxis appears to prevent TB and can be safely used in all LT recipients. However, prospective studies using large sample sizes are required to confirm these findings.

Heterogeneous vascular patterns in renal cell carcinomas.

The present study proposes a classification of renal cancer tumor blood vessels according to their morphology and maturation grade. We identified four vascular patterns: reticular, diffuse, fasciculated and trabecular. The reticular pattern was present in 63% of cases, being characterized by the predominance of mature CD34+/SMAct+ tumor vessels, highly interconnected. For this pattern, 74% of cases had vascular invasion, and a significant correlation was observed between tumor grade and immature state of tumor vessels (p = 0.022). The diffuse pattern was observed in 23% of cases and was characterized by non-interconnected vessels predominantly of mature CD34+/SMAct+ type and vascular invasion in 64% of cases. Only 8% of cases, had a fasciculate model of vessels distribution, all of them being of mature type, located in the connective axis of papillary renal tumors. For this pattern vascular invasion was found in 50% of cases. In 6% of cases a trabecular pattern was observed and the lowest rate of vascular invasion was registered. We defined here four distinct vascular patterns in renal cell carcinomas showing a strong impact on vascular invasion. A complete morphological and molecular characterization of tumor vessels would be beneficial in elucidating the mechanisms that underlie the ineffectiveness of antiangiogenic/antitumor therapies.

Tacrolimus-Induced Neurotoxicity in Early Post-Liver Transplant Saudi Patients: Incidence and Risk Factors.

BACKGROUND Tacrolimus is a calcineurin inhibitor (CNI) commonly used as an immunosuppressant to prevent the rejection of organ transplants. After liver transplantation, it can cause early neurological complications, known as early calcineurin inhibitor-induced neurotoxicity (ECIIN). Its management requires CNI withdrawal, a measure that can affect post-transplant outcomes, primarily allograft rejection. In addition, it can negatively impact the quality of life. The incidence and risk factor of ECIIN has not been reported in the Saudi population. We investigated the incidence and risk factors of ECIIN after liver transplant in Saudi patients. We also looked at the length of stay in the Intensive Care Unit, hospital, and 30-day mortality as secondary endpoints. MATERIAL AND METHODS This was a retrospective cohort study of adult patients on tacrolimus with mild, moderate, or severe neurological events within the first month after liver transplantation at a single center of patients who meet the inclusion criteria and were over age 14 years. A total of 338 patients were included in the analysis, and the sample size was calculated based on a pilot study. RESULTS Among 338 liver transplantation patients, 63 patients (19%) developed ECIIN. Forty-eight percent of patients had seizures, 23% had agitation, 21% had psychosis, 10% had severe tremors, 13% had confusion, and 6% developed coma. The median time of the incident to develop ECIIN was 9 (IQR: 5-13.5) days after transplant. Thirty-eight patients were managed by switching to cyclosporine, 12 required a reduction in the dose, and 3 were managed temporarily by discontinuing therapy. Autoimmune hepatitis as an underlying liver disease was one of the statistically significant risk factors (P=0.0311). The median length of hospital stay was 31 (IQR: 21-75.5) days, ICU length of stay was 10 (IQR: 5-20.5) days, and 8 patients died within 30 days after transplant. CONCLUSIONS The incidence of ECIIN in Saud Arabia was similar to that reported in other populations with similar risk factors. Electrolyte imbalance, mainly hyponatremia, was significantly associated with developing ECIIN. Therefore, ECIIN may potentially increase hospital and ICU length of stay.

MXene (Ti3C2Tx)/Cellulose Acetate Mixed-Matrix Membrane Enhances Fouling Resistance and Rejection in the Crossflow Filtration Process.

Obstacles in the membrane-based separation field are mainly related to membrane fouling. This study involved the synthesis and utilization of covalently crosslinked MXene/cellulose acetate mixed matrix membranes with MXene at different concentrations (CCAM-0% to CCAM-12%) for water purification applications. The membranes' water flux, dye, and protein rejection performances were compared using dead-end (DE) and crossflow (CF) filtration. The fabricated membranes, especially CCAM-10%, exhibited high hydrophilicity, good surface roughness, significantly high water flux, high water uptake, and high porosity. A significantly higher flux was observed in CF filtration relative to DE filtration. Moreover, in CF filtration, the CCAM-10% membrane exhibited 96.60% and 99.49% rejection of methyl green (MG) and bovine serum albumin (BSA), respectively, while maintaining a flux recovery ratio of 67.30% and an irreversible fouling ratio at (Rir) of 32.70, indicating good antifouling performance. Hence, this study suggests that covalent modification of cellulose acetate membranes with MXene significantly improves the performance and fouling resistance of membranes for water filtration in CF mode relative to DE mode.

Saudi consensus recommendations on the management of multiple sclerosis: MS management in children and adolescents.

Multiple sclerosis (MS) most commonly presents in young adults, although 3-5% of patients develop MS prior to the age of 18 years. The new and comprehensive consensus for the management of MS in Saudi Arabia includes recommendations for the management of MS and other CNS inflammatory demyelinating disorders in pediatric and adolescent patients. This article summarizes the key recommendations for the diagnosis and management of these disorders in young patients. Pediatric and adult populations with MS differ in their presentation and clinical course. Careful differential diagnosis is important to exclude alternative diagnoses such as acute disseminated encephalomyelitis (ADEM) or neuromyelitis optica spectrum disorders (NMOSD). The diagnosis of MS in a pediatric/adolescent patient is based on the 2017 McDonald diagnostic criteria, as in adults, once the possibility of ADEM or NMOSD has been ruled out. Few data are available from randomized trials to support the use of a specific disease-modifying therapy (DMT) in this population. Interferons and glatiramer acetate are preferred initial choices for DMTs based on observational evidence, with the requirement of a switch to a more effective DMT if breakthrough MS activity occurs.

[Intramural intestinal hematoma--a complication of the oral anticoagulant therapy]. / Hematom intestinal intramural, complicatie a tratamentului anticoagulant oral.

AIM: The presentation of a rare complication of oral anticoagulant treatment involving abdominal surgery. MATERIAL AND METHOD: A 59 years old patient who received oral anticoagulant treatment with Warfarine for repeated episodes of thrombosis of the lower limbs, suddenly develops an occlusive abdominal simptoms, which did not submit under conservative treatment. Biologically the clotting times were modified and the abdominal CT showed lesions of the first jejunal loop. RESULTS: During surgery an amount of blood was found in abdominal cavity and a large haematoma of the first jejunal loop which required resection. The postoperative evolution was simple with discharge in the 12th day, surgically cured. CONCLUSIONS: 1. Intramural intestinal haematoma is a rare, but possible complication of the oral anticoagulant treatment. 2. Precise diagnosis is possible, avoiding unnecessary surgical intervention because the complication is treatable using conservative therapy. 3. Surgical intervention is required in case of a sudden onset, imprecise diagnosis and unfavorable evolution which could point associated intraabdominal lesions.

Layered zinc hydroxide as an adsorbent for phosphate removal and recovery from wastewater.

At present, phosphate removal and recovery from wastewater is gaining wide attention due to the dual issues of eutrophication, caused by the increased production of algae, and universal phosphorus scarcity. In this study, a layered zinc hydroxide (LZH) was synthesized by a simple precipitation method and characterized via various techniques. Experiments investigating the effect of contact time, pH, LZH dose, initial phosphate concentration, and co-existing ions on phosphate adsorption were conducted. LZH exhibited a high phosphate adsorption capacity (135.4 mg g-1) at a neutral pH. More than 50% of phosphate was removed within the first 60 s of contact time at an initial phosphate concentration of 5 mg L-1. Phosphate removal using the as-prepared LZH adsorbent was also tested in real treated sewage effluent reducing the residual phosphate amount to levels inhibiting to the growth of algae. Furthermore, phosphate desorption from LZH was investigated using acetic acid and sodium hydroxide regenerants which showed to be very effective for phosphate recovery.

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe.

[Intestinal stromal tumors, rare cause of lower gastrointestinal bleeding. Case report]. / Tumora intestinala stromala, cauza rara de hemoragie digestiva inferioara. Caz clinic.

Gastrointestinal stromal tumors represent a heterogeneous group of mesenchymal tumors that can develop throughout the gastrointestinal tract. We present the clinical case of a patient with such malignancies occurred in the proximal jejunum and clinically manifested by a severe digestive hemorrhage with hemorrhagic shock and severe posthemorrhagic anemia. Pre-operative diagnosis was possible only through the Entero-MRI. The evolution was favorable after surgical extirpation. It's being discussed particular aspects of this lesion's entity and post-operative optimal attitude in this case.

Correction to: Abstracts : 31st European Congress of Pathology.

In E-Poster Sessions of the published abstract, the authors' affiliations as well as the abstract text were incorrectly presented. The correct abstract and the author's affiliations are shown in full in this article.

Granular cell tumor of the penis shaft: case report and literature review.

INTRODUCTION: Granular cell tumors (GCT) are uncommon soft tissue neoplasms of presumed neural origin that rarely involve the male external genitalia. Penile lesions are distinctly uncommon with less than 20 cases reported till now. OBJECTIVE: In the present paper we describe the clinicopathological and immunohistochemical findings in a case of GCT of the penis shaft in a 31-years-old man. RESULTS AND CONCLUSIONS: On physical examination the patient was found to have a small ovoid mass, 20 x 10 mm in diameter, at the left postero-lateral area of the penis' base. The mass was firm on palpation with no fixation on the neighboring tissues. The lesion was completely excised under loco-regional anesthesia. The surgical specimen was an ovoid, gray-white, elastic mass, of 10 x 5 mm. Microscopically, the tumor was moderately cellular and was composed of polygonal-shaped cells with abundant granular eosinophilic cytoplasm. Tumor cells were disposed in nests, cords, and trabeculae and showed perineural invasion. The tumor presented bland cytological features with only focal slight nucleo-megaly. Mitotic activity was undetectable. The tumor cells showed diffuse immunohistochemical expression for S100 protein. At 6 month after surgery the patient was free of persistent/recurrent disease or metastatic spread of the tumor. We discuss the clinical, histo-immunohistochemical and therapeutical features of this unusual penile tumor, the single one encountered in the Department of Pathology from Timisoara County Hospital and, to our knowledge, the only one reported in the Romanian medical literature.

Adsorption of phosphate on iron oxide doped halloysite nanotubes.

Excess phosphate in water is known to cause eutrophication, and its removal is imperative. Nanoclay minerals are widely used in environmental remediation due to their low-cost, adequate availability, environmental compatibility, and adsorption efficiency. However, the removal of anions with nanoclays is not very effective because of electrostatic repulsion from clay surfaces with a net negative charge. Among clay minerals, halloysite nanotubes (HNTs) possess a negatively charged exterior and a positively charged inner lumen. This provides an increased affinity for anion removal. In this study, HNTs are modified with nano-scale iron oxide (Fe2O3) to enhance the adsorption capacity of the nanosorbent. This modification allowed for effective distribution of these oxide surfaces, which are known to sorb phosphate via ligand exchange and by forming inner-sphere complexes. A detailed characterization of the raw and (Fe2O3) modified HNTs (Fe-HNT) is conducted. Influences of Fe2O3 loading, adsorbent dosage, contact time, pH, initial phosphate concentration, and coexisting ions on the phosphate adsorption capacity are studied. Results demonstrate that adsorption on Fe-HNT is pH-dependent with fast initial adsorption kinetics. The underlying mechanism is identified as a combination of electrostatic attraction, ligand exchange, and Lewis acid-base interactions. The nanomaterial provides promising results for its application in water/wastewater treatment.

Congenital Esophageal Atresia and Microtia in a Newborn Secondary to Mycophenolate Mofetil Exposure During Pregnancy: A Case Report and Review of the Literature.

BACKGROUND Mycophenolate mofetil (MMF) is one of the most commonly prescribed drugs to prevent organ transplant rejection in combination with calcineurin inhibitors and steroids. It has a different toxicity profile than tacrolimus and cyclosporine.  Gastrointestinal tract disturbances are the most common adverse effects. The use of MMF in pregnant women, however, holds great risk of miscarriage and fetal development defects such as external ear malformation, ocular anomalies, cleft lip and palate, and abnormality of distal limbs, heart, esophagus, and kidneys. Based on post-marketing studies, its pregnancy category was reclassified as category D by the US FDA in 2007. CASE REPORT A 20-year-old woman received a deceased-donor liver transplant for end-stage liver disease secondary to autoimmune hepatitis. She had 3 miscarriages while on MMF. In her fourth pregnancy she was exposed to MMF in the first trimester, which was stopped by week 20 of the pregnancy. Obstetric ultrasound suggested a cephalic presentation fetus with abdominal circumference. Her pregnancy resulted in an infant with tracheoesophageal fistula, esophageal atresia, and a bilateral ear canal atresia (microtia) with normal sensorineural conduction. There were no other congenital abnormalities. Thoracoscopic ligation of fistula and thoracotomy with esophageal repair were performed and a bone-anchored hearing aid for conductive hearing loss was implanted. Here, we report a case of congenital esophageal atresia and microtia secondary to mycophenolate mofetil. CONCLUSIONS MMF should be avoided during pregnancy. Transplanted female patients of reproductive age should receive appropriate counseling.

[An unusual splenic tumor. Littoral cell angioma]. / O tumora splenica neobisnuita. Angiomul cu celule litorale.

Littoral cell angioma is a rare splenic tumor which develops from specialised endothelial cells of the splenic red pulp. Numerous papers published since 1991 when the tumor was firstly described till now were focused on the radiologic characteristics of the lesion. This paper presents the clinical, imaging and morpho-immunohistochemical features of a littoral cell angioma diagnosed in a 51 year - old woman, to our knowledge, the first documented case in the Romanian medical literature. The lesion might be suspected on the basis of the clinical and imaging signs, but the diagnosis of certitude is provided by the gross and microscopic examination supplemented with immunohistochemical methods.

Clinical evaluation of four tumor markers in malignant and benign pleural effusions.

Total sialic acid (TSA), lipid-bound sialic acid (LSA), ferritin and carcinoembryonic antigen (CEA) were evaluated in 55 patients with malignant pleural effusions and in 32 patients with benign (exudative) pleural effusions. No significant differences were found in the pleural fluid TSA, LSA and ferritin levels between malignant and benign conditions. CEA levels in malignant effusions were significantly higher than those in benign effusions (43.13 +/- 72.8 ng/ml versus 2.6 +/- 5.56 ng/ml, p less than 0.01). At a cut-off level of 5 ng/ml, 60% of the patients with cancer showed elevated pleural fluid CEA levels. The specificity and diagnostic accuracy of CEA in distinguishing malignant from benign pleural exudates were both very high (91% and 71% respectively). Therefore, of the four markers investigated, only CEA could be a valuable tool in the detection of pleural malignancy.

Five tumor markers in lung cancer: significance of total and "lipid"-bound sialic acid.

Total sialic acid (TSA) and "lipid-bound" sialic acid (LSA) were evaluated in comparison to carcinoembryonic antigen (CEA) and ferritin and neuron specific enolase (NSE) in 152 untreated patients with primary lung cancer, 107 benign pulmonary disease patients and 207 notmal controls. The mean concentrations of TSA, LSA and CEA in lung cancer patients, were significantly higher than in benign and normal controls (p less than 0.001), while the mean ferritin and NSE levels were significantly higher than in normal controls only (p less than 0.001). At the designated cut-off serum levels, sensitivities of the five markers for lung cancer were in decreasing order: TSA 86.5% (greater than 80 mg/dL), LSA 77% (greater than 20 mg/dL), CEA 46.4% (greater than 5 ng/mL), ferritin 36% (greater than 300 ng/mL) and NSE 34.5% (greater than 12.5 ng/mL). Using the benign pulmonary values as negative controls the specificity of each marker was as follows: CEA 88%, ferritin 72%, NSE 58%, TSA 44% and LSA 44%. In small cell lung cancer (SCLC) patients, NSE mean concentrations and sensitivity were significantly higher than in non-small lung cancer (NSCLC) patients (9.63 +/- 4.4 versus 23.54 +/- 16.9, p less than 0.001 and 74% versus 21.4% respectively). While in NSCLC patients only CEA levels correlated well with the stage of the disease, in SCLC patients concentrations of TSA, LSA and ferritin were significantly higher in extensive than in limited disease stages. These preliminary data suggest that, although TSA and LSA are highly sensitive markers in lung cancer, their specificity is low.

Immunohistochemical expression of prostate specific antigen (PSA) in benign and malignant tumors of the prostate.

The immunohistochemical (IHC) expression of PSA in tissue fragments has been analysed in 25 patients with benign prostatic hypertrophy (BPH) and in 50 patients with prostatic carcinoma. The fragments were obtained by transurethral resection and transvesical adenomectomy. Morphology was studied by hematoxylin-eosin and Gömöri's trichrome staining. For immunohistochemical study anti-PSA monoclonal antibodies (DAKO, EPOS) were used. In BPH cases a positive reaction in the cytoplasm of secretory luminal cells was noticed; the reaction was negative in basal and urothelial cells, in foci of squamous metaplasia and in the cells of mucous gland metaplasia. All the classic types of prostatic carcinoma, regardless of the degree of differentiation showed positive reaction with various intensity and distribution. A positive focal reaction was noticed in two ductal carcinomas of endometrioid type. The reaction was negative in transitional, epidermoid and small cell carcinoma. Though less useful in differentiating benign from malignant lesions, this method may contribute to the differential diagnosis of particular forms of prostatic tumors.

Prognostic significance of neuroendocrine differentiation in carcinoma of the prostate.

Biopsies taken by core-needle biopsy and/or transurethral resection to 68 patients with prostatic neoplasia stage III and IV, were studied morphohistochemically. Morphological observations showed high incidence of mixed histopathological forms. The Churukian-Schenk and Garvey silver impregnations were used in order to identify associated neuroendocrine differentiations. Three cases presented monomorphic small cell proliferation which contained numerous argyrophilic cytoplasmic granulations. The prognosis in these cases was poor--the patients died because of neoplastic extension within 5 to 9 months following diagnosis. Neuroendocrine cells were identified in 15 cases, 6 of which presented a malignant pattern. Taking into consideration the hormonal resistance of malignant cells with argyrophilic granulations, the necessity of chemotherapy associated to hormonotherapy is discussed.

The first international residency program accredited by the American Society of Health-System Pharmacists.

The processes by which the pharmacy residency program at King Faisal Specialist Hospital and Research Centre-Riyadh, Saudi Arabia became the first American Society of Health-System Pharmacists (ASHP) accredited program outside the United States is described. This article provides key points for a successful program for other pharmacy residency programs around the world. Additionally, it points out the need for establishing international standards for pharmacy residency programs.