Empathy among Saudi Residents at a Tertiary Academic Center during the COVID-19 Pandemic and Its Association with Perceived Stress.

Background and Objectives: Empathy is an important attribute of a healthy doctor−patient relationship. Although multiple studies have assessed empathy in different countries, little is known about its levels among Saudi residents and its association with perceived stress. Objectives: To assess the levels of empathy and to identify if there is an association with stress in general and across the demographic and training characteristics of residents. Materials and Methods: A cross-sectional questionnaire-based study was carried out from December 2020 to March 2021 among residents training at a tertiary academic center in Riyadh, Saudi Arabia. Empathy and perceived stress were measured using the Jefferson Scale of Empathy (JSE) and the Perceived Stress Scale (PSS). Results: A total of 229 residents participated. The mean JSE score was 105.25 ± 15.35. The mean JSE scores were significantly higher among residents training in pediatrics (mean difference (MD) = 17.35, p < 0.001), family medicine (MD = 12.24, p = 0.007), and medical specialties (MD = 11.11, p = 0.012) when compared with surgical specialties and anesthesia. In addition, residents who worked 1−4 on-calls per month had a higher mean JSE score (MD = 11.23, p = 0.028) compared with those who worked 7 or more on-calls. Lastly, no correlation between empathy and perceived stress was detected in the whole sample (r = −0.007, p = 0.913); however, there was a correlation among residents training in medical specialties (r = −0.245, p = 0.025). Conclusion: Residents in our study had empathy levels comparable with Asian but lower than Western residents. We recommend qualitative studies that explore potential factors that might affect empathy among residents and studying the association between empathy and perceived stress among medical residents. Postgraduate curricula should incorporate interventions that foster a more empathetic doctor−patient relationship.

Procedure-specific Training for Robot-assisted Distal Pancreatectomy.

OBJECTIVE: To train practicing surgeons in robot-assisted distal pancreatectomy (RADP) and assess the impact on 5 domains of healthcare quality. BACKGROUND: RADP may reduce the treatment burden compared with open distal pancreatectomy (ODP), but studies on institutional training and implementation programs are scarce. METHODS: A retrospective, single-center, cohort study evaluating surgical performance during a procedure-specific training program for RADP (January 2006 to September 2017). Baseline and unadjusted outcomes were compared "before training" (ODP only; June 2012). Exclusion criteria were neoadjuvant therapy, vascular- and unrelated organ resection. Run charts evaluated index length of stay (LOS) and 90-day comprehensive complication index. Cumulative sum charts of operating time (OT) assessed institutional learning. Adjusted outcomes after RADP versus ODP were compared using a secondary propensity-score-matched (1:1) analysis to determine clinical efficacy. RESULTS: After screening, 237 patients were included in the before-training (133 ODP) and after-training (24 ODP, 80 RADP) groups. After initiation of training, mean perioperative blood loss decreased (-255 mL, P<0.001), OT increased (+65 min, P < 0.001), and median LOS decreased (-1 day, P < 0.001). All other outcomes remained similar (P>0.05). Over time, there were nonrandom (P < 0.05) downward shifts in LOS, while comprehensive complication index was unaffected. We observed 3 learning curve phases in OT: accumulation (<31 cases), optimization (case 31-65), and a steady-state (>65 cases). Propensity-score-matching confirmed reductions in index and 90-day LOS and blood loss with similar morbidity between RADP and ODP. CONCLUSION: Supervised procedure-specific training enabled successful implementation of RADP by practicing surgeons with immediate improvements in length of stay, without adverse effects on safety.

Yttrium-90 radioembolization using MIRD dosimetry with resin microspheres.

OBJECTIVE: To review the technical feasibility of resin microsphere (SIR-Spheres®) yttrium-90 radioembolization prescribed using the medical internal radiation dose (MIRD) model. METHODS: All radioembolization procedures for hepatic malignancies using resin microspheres with MIRD model between November 2015 and February 2019 were included in this IRB-approved study (n = 60). Student's T test was used to compare prescribed activity based on MIRD and BSA models. Adverse events were assessed immediately, 30 days, and 6 months post-treatment. RESULTS: Sixty radioembolizations were performed in 54 patients (age 68 ± 9 years, 48-87 years, 35% female). Mean prescribed activity calculated by the MIRD model (target absorbed dose 120-200 Gy for primary and 80-200 Gy for metastatic liver cancers) was 1.7 GBq (0.3-6.4) compared with 0.6 GBq (0.12-2.1) if BSA had been used (p < 0.0001). The prescribed activity was successfully delivered in 93% (56/60) treatments. Prophylactic embolization and anti-reflux catheters were used in 20% (12/60) and 5% (3/60) treatments, respectively. No immediate post-procedural complications occurred. Abdominal pain was the most common clinical Grade 3 CTCAE in 30 days (10%) and 6 months (12%). Radiation pneumonitis occurred in 3 (5%) patients but no radiation-induced gastric ulcer or radiation-induced liver disease occurred. CONCLUSION: MIRD dosimetry results in higher prescribed activity compared with BSA dosimetry with resin microspheres. MIRD prescribed activity with target absorbed doses up to 200 Gy can be successfully administered without prophylactic embolization in selected patients. KEY POINTS: •MIRD dosimetry results in higher prescribed activity compared with BSA dosimetry for radioembolization. •MIRD dosimetry can be used for yttrium-90 resin microsphere radioembolization with acceptable safety profile.

The possible role of methylglyoxal metabolism in cancer.

Tumours reprogram their metabolism to acquire an evolutionary advantage over normal cells. However, not all such metabolic pathways support energy production. An example of these metabolic pathways is the Methylglyoxal (MG) one. This pathway helps maintain the redox state, and it might act as a phosphate sensor that monitors the intracellular phosphate levels. In this work, we discuss the biochemical step of the MG pathway and interrelate it with cancer.

Metabolic Shifts as the Hallmark of Most Common Diseases: The Quest for the Underlying Unity.

A hyper-specialization characterizes modern medicine with the consequence of classifying the various diseases of the body into unrelated categories. Such a broad diversification of medicine goes in the opposite direction of physics, which eagerly looks for unification. We argue that unification should also apply to medicine. In accordance with the second principle of thermodynamics, the cell must release its entropy either in the form of heat (catabolism) or biomass (anabolism). There is a decreased flow of entropy outside the body due to an age-related reduction in mitochondrial entropy yield resulting in increased release of entropy in the form of biomass. This shift toward anabolism has been known in oncology as Warburg-effect. The shift toward anabolism has been reported in most diseases. This quest for a single framework is reinforced by the fact that inflammation (also called the immune response) is involved in nearly every disease. This strongly suggests that despite their apparent disparity, there is an underlying unity in the diseases. This also offers guidelines for the repurposing of old drugs.

Antiproliferative Isoprenoid Derivatives from the Red Sea Alcyonacean Xenia umbellata.

From the soft coral Xenia umbellata, seven isoprenoid derivatives were isolated, including a new xenicane diterpene, xeniolide O (5) and a new gorgostane derivative gorgst-3ß,5α,6ß,11α,20(S)-pentol-3-monoacetate (7), along with three known sesquiterpenes (1-3), a known diterpene (4), and a known steroid (6). The extensive analyses of the NMR, IR, and MS spectral data led to determination of their chemical structures. Compounds 1-7 displayed a cytotoxic effect against breast adenocarcinoma (MCF-7), hepatocellular carcinoma (HepG2), and cervix adenocarcinoma (HeLa), with IC50 values ranging between 1.5 ± 0.1-23.2 ± 1.5; 1.8 ± 0.1-30.6 ± 1.1 and 0.9 ± 0.05-12.8 ± 0.5 µg/mL, respectively. Compound 3 showed potent cytotoxic effects against MCF-7, HepG2, and HeLa with IC50 values = 2.4 ± 0.20, 3.1 ± 0.10 and 0.9 ± 0.05 µg/mL, respectively. Compounds 2, 5, and 7 displayed cytotoxic effect against Hela cells with IC50 values = 12.8 ± 0.50, 6.7 ± 1.00 and 11.5 ± 2.20 µg/mL, respectively. Two DNA binding dyes, acridine orange (AO) and ethidium bromide (EtBr) were used for the detection of viable, apoptotic, and necrotic cells. The early apoptotic cell death was observed in all types of treated cells. The late apoptotic cells were highly present in HepG2 cells. Compounds 5 and 7 induced a high percentage of necrosis towards HepG2 and HeLa cells. The late apoptosis was recorded as a high rate after treatment with 7 on all cancer cells.

Molecular Analysis of the Antibiotic Resistant NDM-1 Gene in Clinical Isolates of Enterobacteriaceae.

BACKGROUND: The emergence of the New Dehli metallo-beta-lactamase (NDM) gene in Enterobacteriaceae is responsible for multidrug resistance responsible for severe infections and serious morbidity in patients. Our study aimed to define the molecular characteristics and antibiogram of the NDM-1 producing Enterobacteriaceae. METHODS: We isolated 370 individual enterobacteria from the clinical specimens collected from the two tertiary hospitals in Sakaka, Saudi Arabia. Bacterial isolation was performed using standard microbiological techniques and the Phoenix and Microscan WalkAway Plus automated analyzers. Bacterial strains were characterized by phenotypic methods and PCR, and DNA sequencing was used for the molecular characterization of NDM genes. RESULTS: The blaNDM gene was detected among the 68 members of the Enterobacteriaceae including a single case of rarely reported Cedecea lapagei. Of these 68, 43 isolates (63.2%) were blaNDM-1 and 25 (36.8%) were blaNDM variants. A statistically significant relationship between the NDM-1 and Klebsiella pneumoniae (p = 0.004) was seen, and the relationship between the NDM variants was significantly associated with Citrobacter freundii (p = 0.02) and Escherichia coli (p = 0.03). The in vitro minimum inhibitory concentrations (MICs) of NDM-producing Enterobacteriaceae revealed a very high rate of antibiotic resistance against several groups of antibiotics. These bacterial strains were less resistant to two aminoglycosides, gentamicin (39; 57.3%) and amikacin (27; 39.7%), and showed minimum resistance to tigecycline (25; 36.8%). CONCLUSIONS: The emergence of a large number of NDM-1 enterobacteria in our study identifies a substantial public concern, both within hospitals and the wider community, and leaves us a narrow choice of therapeutic options: the aminoglycosides, co-trimoxazole, and tigecycline.

Marine-Derived Macrocyclic Alkaloids (MDMAs): Chemical and Biological Diversity.

The curiosity and attention that researchers have devoted to alkaloids are due to their bioactivities, structural diversity, and intriguing chemistry. Marine-derived macrocyclic alkaloids (MDMAs) are considered to be a potential source of drugs. Trabectedin, a tetrahydroisoquinoline derivative, has been approved for the treatment of metastatic soft tissue sarcoma and ovarian cancers. MDMAs displayed potent activities that enabled them to be used as anticancer, anti-invasion, antimalarial, antiplasmodial, and antimicrobial. This review presents the reported chemical structures, biological activities, and structure-activity relationships of macrocyclic alkaloids from marine organisms that have been published since their discovery until May 2020. This includes 204 compounds that are categorized under eight subclasses: pyrroles, quinolines, bis-quinolizidines, bis-1-oxaquinolizidines, 3-alkylpiperidines, manzamines, 3-alkyl pyridinium salts, and motuporamines.

Complications After Upper Extremity Surgery in Solid Organ Transplant Patients.

PURPOSE: To determine the rate of and risk factors for complications in solid organ transplant (SOT) patients who have had surgery of the upper extremity. METHODS: All SOT recipients who had an upper extremity procedure performed by 1 of 6 surgeons at our institution were identified from 2006 to 2018. Demographic data, transplant date and type, upper extremity surgery procedure and date, antirejection medications, American Society of Anesthesiologists Physical Status Classification System (ASA) score, and complications were recorded. Complications were defined as any surgical complication within 1 year and any medical complication within the first 30 days after surgery. Complications were categorized according to the Clavien-Dindo classification system. RESULTS: Fifty-one upper extremity procedures in 32 SOT patients were included. Of the 51 procedures, 21 were complicated, for an overall complication rate of 41%. Surgical complications occurred equally before and after 30 days with infection being the most common. Only 1 of the procedures resulting in surgical site infection had an implant (temporary K-wire fixation). The majority of complications were grade II, and there were no grade IV or V complications. Age, ASA score, type or number of SOT, and immunosuppressive regimens were similar between complicated and noncomplicated procedures. Procedures involving male patients were more likely to be complicated than those involving female patients. CONCLUSIONS: Complications after upper extremity operations are common in SOT patients, and surgical complications often occur after 30 days. Surgeons should counsel this population that they carry a higher complication risk than the general population and may require longer-term monitoring after surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Synthesis and in vitro antitumor activity of novel acylspermidine derivative N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide (AAHD) against HepG2 cells.

Naturally occurring polyamines like Putrescine, Spermidine, and Spermine are polycations which bind to the DNA, hence stabilizing it and promoting the essential cellular processes. Many synthetic polyamine analogues have been synthesized in the past few years, which have shown cytotoxic effects on different tumours. In the present study, we evaluated the antiproliferative effect of a novel, acylspermidine derivative, (N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide) (AAHD) on HepG2 cells. Fluorescence staining was performed with nuclear stain (Hoechst 33342) and acridine orange/ethidium bromide double staining. Dose and the time-dependent antiproliferative effect were observed by WST-1 assays, and radical scavenging activity was measured by ROS. Morphological changes such as cell shrinkage & blebbing were analyzed by fluorescent microscopy. It was found that AAHD markedly suppressed the growth of HepG2 cells in a dose- and time-dependent manner. It was also noted that the modulation of ROS levels confirmed the radical scavenging activity. In the near future, AAHD can be a promising drug candidate in chalking out a neoplastic strategy to control the proliferation of tumour cells. This study indicated that AAHD induced anti-proliferative and pro-apoptotic activities on HCC. Since AAHD was active at micromolar concentrations without any adverse effects on the healthy cells (Fibroblasts), it is worthy of further clinical investigations.

Early Neurodevelopmental Outcomes in Children with Hypoplastic Left Heart Syndrome and Related Anomalies After Hybrid Procedure.

The hybrid strategy is one approach to single ventricle palliation. In this study, we reported neurodevelopment at 12 months for two cohorts of children managed with the hybrid and clinical factors associated with neurodevelopment in the entire sample. We performed a retrospective study of children with single ventricle who had undergone a neonatal hybrid procedure. One group included infants with hypoplastic left heart syndrome (HLHS); another group included infants with non-HLHS single ventricle. Neurodevelopment was assessed with 12-month Bayley III. Parametric and non-parametric statistics were used for analysis. Nine infants with HLHS and 15 with non-HLHS were identified. Abnormal neurodevelopment was identified in 11 of 24 (46%), primarily motor (46%). Development did not differ between groups. In the whole sample, higher lactate levels were associated with lower cognitive scores (p = 0.04). Fewer mechanical ventilation days were associated with higher cognitive scores (p = 0.05) after Stage 1 and higher motor scores after Stage 2. Shorter ICU length of stay (p = 0.01), shorter hospital length of stay (p = 0.01), and fewer complications (p = 0.01) after stage 2 were associated with higher motor scores. Higher cognitive (p = 0.02) and language (p = 0.002) scores were associated with higher weight at 12 months. In the largest cohort of single ventricle children treated with neonatal hybrid palliation yet reported, significant neurodevelopmental impairment was identified. No differences in neurodevelopment were found between children with HLHS and those with non-HLHS variants. A multicenter trial is needed to test differences in neurodevelopment between hybrid and Norwood approaches.

Hydrogen Ion Dynamics of Cancer and a New Molecular, Biochemical and Metabolic Approach to the Etiopathogenesis and Treatment of Brain Malignancies.

The treatment of cancer has been slowly but steadily progressing during the last fifty years. Some tumors with a high mortality in the past are curable nowadays. However, there is one striking exception: glioblastoma multiforme. No real breakthrough has been hitherto achieved with this tumor with ominous prognosis and very short survival. Glioblastomas, being highly glycolytic malignancies are strongly pH-dependent and driven by the sodium hydrogen exchanger 1 (NHE1) and other proton (H+) transporters. Therefore, this is one of those pathologies where the lessons recently learnt from the new pH-centered anticancer paradigm may soon bring a promising change to treatment. This contribution will discuss how the pH-centric molecular, biochemical and metabolic perspective may introduce some urgently needed and integral novel treatments. Such a prospective therapeutic approach for malignant brain tumors is developed here, either to be used alone or in combination with more standard therapies.

Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH.

As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models. This treatment, in combination with conventional chemotherapy, has yielded extremely encouraging results in glioblastoma, brain metastasis and lung cancer. Randomized trials are necessary to confirm these preliminary data. The major limitation is the fact that the combination of α-lipoic acid and hydroxycitrate can only be effective if the mitochondria are still present and/or functional. That may not be the case in the most aggressive tumors. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Concomitant correction of this alkalosis may be a very effective treatment in case of mitochondrial failure.

Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection.

The phase 2, open-label ACCORDION (ClinicalTrials.gov: NCT02349048) study investigated the efficacy, safety and pharmacokinetics of a 6- or 8-week regimen of simeprevir, daclatasvir and sofosbuvir in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype (GT) 1 infection and either early-stage fibrosis or compensated cirrhosis. Patients were assigned to treatment groups according to their fibrosis stage. Early-stage fibrosis: simeprevir 150 mg, daclatasvir 60 mg, sofosbuvir 400 mg once daily for 6 weeks; compensated cirrhosis: same regimen for 8 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety, tolerability and pharmacokinetics of simeprevir, daclatasvir and sofosbuvir were investigated. Sixty-eight patients were treated (6-week group: n = 59; 8-week group: n = 9). SVR12 was achieved by 86.4% (51/59) of patients with early-stage fibrosis and by 100% (9/9) of patients with cirrhosis. The main reason for not achieving SVR12 in the 6-week group was viral relapse (11.9%; 7/59). One patient had on-treatment failure due to an early withdrawal (lost to follow-up due to incarceration). One patient with SVR12 in the 6-week group had a late viral relapse at post-treatment week 24. No clinically significant drug-drug interactions were observed. Adverse events were reported in 63.2% of patients (43/68) and were mainly grade 1/2. None of these led to treatment discontinuation. The 3 direct-acting antiviral regimens of simeprevir, daclatasvir and sofosbuvir were safe and well tolerated in treatment-naïve, HCV GT1-infected patients with early-stage fibrosis or compensated cirrhosis.

Population data of 21 autosomal STR loci in the Hausa, Igbo and Yoruba people of Nigeria.

The three major ethnic groups of Nigerian population namely the Hausa, Igbo and Yoruba make up 29, 21 and 18% of the total population, respectively. To provide genetic information necessary for forensic analysis, this study was carried out to determine STR allele frequencies in 102 Hausa, 128 Igbo and 134 Yoruba individuals in Nigeria using 21 STR loci including the 20 CODIS (Combined DNA Index System) loci plus SE33.

Correction to: Population data of 21 autosomal STR loci in the Hausa, Igbo and Yoruba people of Nigeria.

In the original paper author Alani Sulaimon Akanmu was erroneously omitted from the author list. Prof. Akanmu has now been added as 4th author. Prof. Akanmu acted as an academic supervisor of the study and additionally contributed to the publication by reading, commenting and editing the manuscript.

Isolation, antimicrobial and antitumor activities of a new polyhydroxysteroid and a new diterpenoid from the soft coral Xenia umbellata.

A new C-30 steroid, 3ß-,5α-,6ß-,11α-,20ß-pentahydroxygorgosterol (1), and a new diterpenoid, xeniumbellal (2), along with three known aromadendrane-type sesquiterpenes, aromadendrene (3), palustrol (4) and viridiflorol (5), were isolated from the soft coral Xenia umbellata. Chemical structures were determined by analyzing their NMR and MS data. The antimicrobial and antitumor activities of the isolated compounds were examined. Both 1 and 2 showed moderate antibacterial activities, especially against the multidrug-resistant Acinetobacter baumannii (MIC 0.22 and 0.28 mM, respectively); while 2 showed antitumor activity against a lymphoma cell line with LD50 0.57 mM and was nontoxic to Artemia salina at all tested concentrations up to about 4 mM.

Isolaurenidificin and Bromlaurenidificin, Two New C15-Acetogenins from the Red Alga Laurencia obtusa.

Chromatographic fractionation of the CH2Cl2/MeOH extract of the Red Sea red alga Laurencia obtusa gave two new hexahydrofuro[3,2-b]furan-based C15-acetogenins, namely, isolaurenidificin (1) and bromlaurenidificin (2). The chemical structures were elucidated based on extensive analyses of their spectral data. Compounds 1 and 2 showed no toxicity (LC50 > 12 mM) using Artemia salina as test organism. Both compounds showed weak cytotoxicity against A549, HepG-2, HCT116, MCF-7, and PC-3 cells, however, they exhibited a relatively potent cytotoxic activity against peripheral blood neutrophils. This can be attributed partly to induction of apoptosis.

Synthetic Phenolic Antioxidants and Their Metabolites in Indoor Dust from Homes and Microenvironments.

Synthetic phenolic antioxidants (SPAs), including 2,6-di-tert-butyl-4-hydroxytoluene (BHT), are extensively used in food, cosmetic and plastic industries. Nevertheless, limited information is available on human exposures, other than the dietary sources, to SPAs. In this study, occurrence of 9 SPAs and their metabolites/degradation products was determined in 339 indoor dust collected from 12 countries. BHT was found in 99.5% of indoor dust samples from homes and microenvironments at concentrations that ranged from < LOQ to 118 µg/g and 0.10 to 3460 µg/g, respectively. This is the first study to measure BHT metabolites in house dust (0.01-35.1 µg/g) and their concentrations accounted for 9.2-58% of the sum concentrations (∑SPAs). 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO), 2,6-di-tert-butyl-4-(hydroxymethyl)phenol (BHT-OH), 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q) were the major derivatives of BHT found in dust samples. The concentrations of gallic acid esters (gallates) in dust from homes and microenvironments ranged from < LOQ to 18.2 and < LOQ to 684 µg/g, respectively. The concentrations and profiles of SPAs varied among countries and microenvironments. Significantly elevated concentrations of SPAs were found in dust from an e-waste workshop (1530 µg/g). The estimated daily intake (EDI) of BHT via house dust ingestion ranged from 0.40 to 222 ng/kg/d (95th percentile).