Formulation and evaluation of Fluconazole Nanosuspensions: In vitro characterization and transcorneal permeability studies.

The aim in this study was to develop and evaluate a nanofluconazole (FLZ) formulation with increased solubility and permeation rate using nanosuspensions. The FLZ nanosuspensions were stabilized using a variety of stabilizing agents and surfactants in various concentrations. The FLZ nanosuspension was characterized in vitro using particle size, zeta potential, X-ray powder diffraction (XRPD), and solubility. In addition, the ex vivo ocular permeation of FLZ through a goat cornea was analyzed. The results showed that the particle size of all nanosuspension formulations was in the nanometer range from 174.5 ± 1.9 to 720.2 ± 4.77 nm; that of the untreated drug was 18.34 µm. The zeta potential values were acceptable, which indicated suitable stability for formulations. The solubility of the nanosuspensions was up to 5.7-fold higher compared with that of the untreated drug. The results of the ex vivo ocular diffusion of the FLZ nanosuspensions showed the percentage of FLZ penetrating via the goat cornea increased after using Kollicoat to stabilize the nanosuspension formulation. Consequently, when using a nanosuspension formulation of Kollicoat, the antifungal activity of the drug strengthens.

Utilization of Waste Eggshell Powder as an Excipient for Vitamin D3 Tablet Preparation.

Keeping in mind the health scenario in Kingdom of Saudi Arabia with respect to vitamin D3 (VD3) deficiency and its significant role in calcium homeostasis and human metabolism, this research is exploring the combination of eggshell (as a source of calcium) and VD3 as a very economical solution for this problem. Eggshells from local restaurant were collected, washed, ground, sieved, and characterized by Fourier transforms infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET) techniques. The results of FTIR, SEM, DSC, XRD, and BET indicate that eggshell powder (ESP) was properly processed. Directly compressed tablets containing 2.5 mg of VD3 (equivalent to 50,000 IU), that are based on the use of ESP as tablet filler, were manufactured based on mixing Avicel PH 101 with ESP in different ratios (9:1, 1:1, and 1:9) in addition to the use of both Avicel PH 101 and ESP alone as tablet filler. Tablets properties were evaluated according to USP30-NF25 pharmacopoeia tests in terms of weight variation test, drug content uniformity, tablet hardness, tablet friability, tablet disintegration, and in vitro dissolution profile. The VD3 contents were found to be 98.77-102.35% in all formulations. After 90 min of study, all formulations showed in vitro drug release content in the range of 99.29-101.05%. All of the tested parameters of ESP tablets were similar to those of commercial Avicel PH 101. All of the tested properties of tablets with ESP as a filler were found to be within the acceptable limits of the pharmacopeia recommendations. Therefore, ESP could be exploited for its use as a filler in direct compression tablets.

Dermoscopy-assisted prevalence of hair loss after COVID-19 vaccination among an Egyptian population: a cross-sectional study.

ABSTACT: BACKGROUND: Coronavirus disease (COVID-19) currently named SARS-CoV-2 is a contagious disease caused by a coronavirus; incompatible data are present on the possible relationship among COVID-19 vaccines and hair loss. AIMS: The objective of the current study was to assess dermoscopically the prevalence of hair loss among an Egyptian population following COVID-19 vaccination. METHODS: A total of 2000 participants were enrolled in this cross-sectional study. Adult males and females who received one of recognized COVID-19 vaccine were included, irrespective of the status of previous COVID-19 infection. Those who were aged less than 18 years or above 60 years were excluded. Furthermore, subjects self-reporting hair loss were assessed by dermoscopy. RESULTS: Among the studied cases, n = 478 (23.9%) complained of hair loss following vaccination. The majority of cases noticed their hair loss during the first 2 months post-vaccination (n = 215 after the first month and n = 158 after the 2nd month respectively). CONCLUSION: We reported prevalence of post-vaccination hair fall that was confirmed by trichoscopy and which affected approximately one quarter of participants who received COVID-19 vaccines. Other factors, such as stress and infection, cannot be excluded and remain to be further investigated by larger multicenter studies.

A novel antibacterial approach of Cecropin-B peptide loaded on chitosan nanoparticles against MDR Klebsiella pneumoniae isolates.

Egypt has witnessed the emergence of multidrug-resistant (MDR) Klebsiella pneumoniae, which has posed a serious healthcare challenge. The proper treatment choice for MDR-KP infections is not well determined which renders the problem more complicated, thus making the control of such infections a serious challenge for healthcare professionals. This study aims to encapsulate the cationic antimicrobial peptide; Cecropin-B (Cec-B), to increase its lifetime, drug targeting, and efficacy and study the antimicrobial effect of free and encapsulated recombinant rCec-B peptide on multidrug-resistant K. pneumoniae (MDR-KP) isolates. Fifty isolates were collected from different clinical departments at Theodore Bilharz Research Institute. Minimal inhibitory concentrations (MICs) of rCec-B against MDR-KP isolates were determined by the broth microdilution test. In addition, encapsulation of rCec-B peptide into chitosan nanoparticles and studying its bactericidal effect against MDR-KP isolates were also performed. The relative expression of efflux pump and porin coding genes (ArcrB, TolC, mtdK, and Ompk35) was detected by quantitative PCR in treated MDR-KP bacterial isolates compared to untreated isolates. Out of 60 clinical MDR isolates, 50 were MDR-KP. 60% of the isolates were XDR while 40% were MDR. rCec-B were bactericidal on 21 isolates, then these isolates were subjected to treatment using free nanocapsule in addition to the encapsulated peptide. Free capsules showed a mild cytotoxic effect on MDR-KP at the highest concentration. MIC of encapsulated rCec-B was higher than the free peptide. The expression level of genes encoding efflux and porin (ArcrB, TolC, mtdK, and Ompk35) was downregulated after treatment with encapsulated rCec-B. These findings indicate that encapsulated rCec-B is a promising candidate with potent antibacterial activities against drug-resistant K. pneumoniae.

Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery: In Vitro and In Vivo Studies.

Bromocriptine mesylate (BM), primarily ergocryptine, is a dopamine agonist derived from ergot alkaloids. This study aimed to formulate chitosan (CS)-coated poly ε-caprolactone nanoparticles (PCL NPs) loaded with BM for direct targeting to the brain via the nasal route. PCL NPs were optimized using response surface methodology and a Box-Behnken factorial design. Independent formulation parameters for nanoparticle attributes, including PCL payload (A), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) concentration (B), and sonication time (C), were investigated. The dependent variables were nanoparticle size (Y1), zeta potential (Y2), entrapment efficiency (EE; Y3), and drug release rate (Y4). The optimal formulation for BM-PCL NPs was determined to be 50 mg PCL load, 0.0865% TPGS concentration, and 8 min sonication time, resulting in nanoparticles with a size of 296 ± 2.9 nm having a zeta potential of -16.2 ± 3.8 mV, an EE of 90.7 ± 1.9%, and a zero-order release rate of 2.6 ± 1.3%/min. The optimized BM-PCL NPs were then coated with CS at varying concentrations (0.25, 0.5, and 1%) to enhance their effect. The CS-PCL NPs exhibited different particle sizes and zeta potentials depending on the CS concentration used. The highest EE (88%) and drug load (DL; 5.5%) were observed for the optimized BM-CS-PCL NPs coated with 0.25% CS. The BM-CS-PCL NPs displayed a biphasic release pattern, with an initial rapid drug release lasting for 2 h, followed by a sustained release for up to 48 h. The 0.25% CS-coated BM-CS-PCL NPs showed a high level of permeation across the goat nasal mucosa, with reasonable mucoadhesive strength. These findings suggested that the optimized 0.25% CS-coated BM-CS-PCL NPs hold promise for successful nasal delivery, thereby improving the therapeutic efficacy of BM.

Possible Role of IL-6R/STAT3/MiRNA-34a Feedback Loop in Osteosarcoma.

OBJECTIVE: Osteosarcoma is considered the most common primary malignant tumor that develops from the primary osteoblasts. MiRNAs are small non-coding RNAs that play a key role in tumorigenesis. The aim of this study was to detect the possible relationship between expression levels of miRNA-34a and levels of Signal transducer and activator of transcription 3 (STAT3) and interleukin-6 receptor (IL-6R) in osteosarcoma and the possible role of this relationship in development of metastases in these patients. METHODS: A total of thirty-six (36) bone samples were included in the study. They were divided into 3 groups: Group (I): Twelve normal bone samples as control group. Group (II): Twelve patients with non-metastatic osteosarcoma. Group (III): Twelve patients with metastatic osteosarcoma. MiRNA-34a expression levels were estimated using qRT-PCR. STAT3 and IL-6R levels were measured by ELISA. RESULTS: Expression level of miRNA-34a was downregulated in osteosarcoma groups compared to control group. STAT3 and IL-6R levels were upregulated in osteosarcoma groups compared to control group. This difference in expression levels was found to be more significant in the metastatic group than the non-metastatic one (P<0.001 each). There was a significant positive correlation between STAT3 and IL-6R (r=0.868, P<0.001), and a significant inverse correlation between IL6 and miRNA-34a (r=-0.993, P<0.001). CONCLUSION: miRNA-34a, STAT3 and IL-6R feedback loop could be a potential target for treatment of osteosarcoma and can be used as prognostic indicator for this disease.

Acute Abdomen Is a Rare Presentation of COVID-19 in the Absence of Respiratory Manifestations: A Case Report.

Mild gastrointestinal symptoms and mild abdominal pain often occur in association with COVID-19. However, acute abdomen and severe abdominal pain warranting urgent surgical treatment are rare. Here we present the case of a 40-year-old man who presented with the clinical picture of a perforated duodenal ulcer. He was eventually found to have COVID-19 and was treated conservatively. In this report, we discuss his course of treatment and review the relevant literature.

Pneumoperitoneum as a Complication of Mechanical Ventilation: A Case Report.

Pneumoperitoneum is defined as the presence of free air in the abdominal cavity. The most common cause of pneumoperitoneum is intestinal perforation, which usually requires surgical intervention. Nonsurgical pneumoperitoneum (NPS) is defined as the presence of free air in the abdominal cavity without visceral perforation by an intrathoracic route, which commonly occurs in patients on mechanical ventilation in intensive care units. NSP, when properly diagnosed, can be successfully treated conservatively without surgery, and intensivists and surgeons should be aware of this entity associated with mechanical ventilation to avoid unnecessary surgical intervention.

Optimization and evaluation of Lisinopril mucoadhesive sustained release matrix pellets: In-vitro and ex-vivo studies.

Lisinopril (LIS) is antihypertensive drug, classified as a class III drug with high water solubility and low permeability. To overcome the low permeability, 32 factorial designs aimed to formulate LIS as a sustained-release (LIS-SR) matrix pellet by extrusion/spheronization. Matrix pellets were composed of wet mass containing Avicel® and polymeric matrix polymers (sodium alginate (SA) and chitosan (CS)). Evaluation of the effect of two independent variables, matrix-forming units (SA and CS) on mean line torque, on pellet size, dissolution rate after 6 h, and mucoadhesion strength of the pellets were assessed using Statgraphics software. The tested formulations (F1-F9) showed that mean line torque ranged from 1.583 to 0.461 Nm, with LIS content in the LIS-SR pellets ranged from 87.9 to 103%, sizes varied from 1906 to 1404 µm and high percentages of drug released from pellets formulations (68.48 to 74.18 %), while the mean zeta potential value of mucoadhesive range from -17.5 to -22.9 mV. The selection of optimized formulation must have the following desirability: maximum peak torque, maximum pellets' particle size, and minimum % LIS release after 6hr. LIS optimized sustained release pellet formula composed of 2,159 % SA and 0.357 % CS was chosen as optimized formula. It's showed a 1.055 Nm mean line torque was responsible for the increased pellet size to 1830.8 µm with decreased release rate 56.2 % after 6 hr, and -20.33 mV average mucin zeta potential. Ex-vivo mucoadhesion studies revealed that that the optimize formulation, exhibited excellent mucoadhesive properties, after 1 h, about 73% of the pellets were still attached to the mucus membrane. Additionally, ex-vivo permeation determination of LIS from the optimized LIS-SR formulation was found to be significantly higher (1.7-folds) as compared to free LIS. In conclusion: LIS-SR matrix pellets, prepared with an extrusion/spheronization have desirable excellent characteristics in-vitro and ex-vivo sustained-release pellet formulation of LIS-SR was able to sustain the release of LIS for up to 8 h.

Serum survivin in acne versus post-acne scarring and the possible effect of isotretinoin therapy on its level.

INTRODUCTION: Acne vulgaris is a common chronic inflammatory disorder of the pilosebaceous unit. Survivin is an apoptosis inhibitor protein, and it contributes crucially to cell cycle regulation. This study measures the serum level of survivin in acne and post-acne scarring patients, and assesses the possible effect of isotretinoin therapy on its level. METHODS: Sixty participants, including 40 acne patients (Group IA, IB), and 20 age- and sex-matched controls (Group II) were included. Group IA included 20 patients with active moderate-to-severe acne without scarring, and this group was further prescribed oral isotretinoin therapy for 3 months. Group IB included 20 patients with post-acne scarring of a duration not more than 6 months, without evident active acne lesions. Serum survivin levels were measured in the three groups using an enzyme-linked immunosorbent assay. RESULTS: There was a statistically significant higher serum survivin level in the acne scar group, followed by the active acne group, than in controls. In addition, there was a statistically significant reduction in survivin levels after treatment, and it was positively correlated with a reduction in the global acne grading system (GAGS) in the active acne group. CONCLUSIONS: Survivin may play a role in the evolution of acne and acne scarring, and it could be a possible target for isotretinoin therapy.

Melatonin Mitigates the Progression of Chemically Induced Hepatocellular Carcinoma in Rats via Targeting Wnt/Β-Catenin Pathway, and Small Noncoding miR-let-7b.

Background: Melatonin, the controlling hormone of the sleep-wake cycle, has acquired attention due to its role in immunomodulation, anti-inflammation, as well as its proapoptotic effects. Wnt/ß-catenin signaling can modulate cancer progression by promoting cell division and migration, while miR-let-7b may inhibit cell growth, migration, and invasion by affecting the function of adaptive immune cells. This work was designed to detect the effect of using melatonin as an immunomodulating therapeutic approach to control the progression of chemically induced hepatocellular carcinoma (HCC). Methods: Thirty male rats were equally divided into control, HCC, and melatonin-HCC groups. Animals in the HCC and melatonin-HCC groups were injected with diethylnitrosamine (intraperitoneal single dose) followed by repeated carbon-tetrachloride subcutaneous injection once weekly for six weeks. Melatonin was given from the first week of the study and continued during the process of HCC induction. Results: In the HCC group, the levels of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and Wnt/ß-catenin expression significantly increased, while there was a downregulation of microRNA Let7b. Melatonin administration reversed these changes, along with an increase in hepatic content of interleukin-2 (IL-2) and caspase-3. Conclusions: Melatonin exerted hepatic immunomodulating changes, in addition to proapoptotic and antiangiogenic effects, illustrated by increased IL-2, caspase-3, and decreased VEGF levels, respectively. Moreover, the use of melatonin during hepatocarcinogenesis positively modulated the disrupted expression of microRNA let7b and Wnt/ß-catenin significantly.

Cecal Volvulus a Rare Cause of Intestinal Obstruction. A Case Report.

Cecal volvulus (CV) is a rare cause of acute intestinal obstruction caused by torsion or twisting of a mobile cecum and ascending colon. Early diagnosis and management are essential to prevent serious complications such as bowel gangrene, cecal perforation, and generalized peritonitis. We report a case of cecal volvulus with impending cecal perforation.

FOXD1-mTOR Signaling Pathway on Oral Squamous Cell Carcinoma and Its Inhibition by Rosemary Extract (Invitro-Study).

BACKGROUND: FOXD1 expression in oral squamous cell carcinoma remains uncovered. The aim was to detect the anticancer effect of Rosemary Extract RE through the evaluation of FOXD1 gene expression in (OSCC) by quantitative PCR. METHODS: OSCC cell line was served as a control group. Moreover, the OSCC cell line (SCC-15) was treated with RE (OSCC/ RE group) at 24, 48, and 72 hs time intervals. We assessed the antioxidant activity of RE by evaluation of lipid peroxidation (MDA) and superoxide dismutase (SOD) levels. The cytotoxic effects of RE were examined by MTT assay. mTOR and LC3 I/II autophagy protein markers were assessed by western blot. Apoptosis activity was assessed. RESULTS: The study results were statistically assessed. Intergroup comparisons were analyzed, whereas intragroup comparisons were conducted utilizing one-way repeated measures ANOVA, followed by multiple pairwise paired t-tests with Bonferroni correction revealed a significant increase of FOXD1 gene expression in the control OSCC group in comparison to the OSCC/RE group (p-value <0.001). A significant decrease of mTOR/LC3I/II proteins expression in the OSCC/RE group compared to the control OSCC group (p-value <0.001). CONCLUSION: FOXD1 can be considred a diagnostic biomarker for OSCC. RE inhibits autophagy of oral human cancer cells via mTOR/LC3I/II-dependent pathways and decrease caspase -3 apoptotic level.

Challenging the Subcostal Incision Scar with the Two-staged Abdominoplasty: An Innovative Approach.

Abdominoplasty is a commonly sought-after procedure due to its life-transforming results, but is limited, as in any other operation, by a number of contraindications. One of these contraindications is a subcostal scar, which may jeopardize blood supply to the upper flap of the abdominoplasty, resulting in skin necrosis. Herein, we challenge this dogma by introducing the two-staged abdominoplasty with the utilization of a delayed flap in a 48-year-old multiparous woman presenting with a Kocher incision of open cholecystectomy, with good results and a complication-free course of 3 postoperative months. We recommend this approach in patients with subcostal scars. However, more research into the utilization of delayed flaps in abdominoplasty should be done to have a more well-founded conclusion.

Reconstructing transmission chains of SARS-CoV-2 amid multiple outbreaks in a geriatric acute-care hospital

BackgroundThere is ongoing uncertainty regarding transmission chains and the respective roles of healthcare workers (HCWs) and elderly patients in nosocomial outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in geriatric settings. MethodsWe performed a retrospective cohort study including patients with nosocomial coronavirus disease 2019 (COVID-19) in four outbreak-affected wards, and all SARS-CoV-2 RT-PCR positive HCWs from a Swiss university-affiliated geriatric acute-care hospital that admitted both Covid-19 and non-Covid-19 patients during the first pandemic wave in Spring 2020. We combined epidemiological and genetic sequencing data using a Bayesian modelling framework, and reconstructed transmission dynamics of SARS-CoV-2 involving patients and HCWs, in order to determine who infected whom. We evaluated general transmission patterns according to type of case (HCWs working in dedicated Covid-19 cohorting wards: HCWcovid; HCWs working in non-Covid-19 wards where outbreaks occurred: HCWoutbreak; patients with nosocomial Covid-19: patientnoso) by deriving the proportion of infections attributed to each type of case across all posterior trees and comparing them to random expectations. ResultsDuring the study period (March 1 to May 7, 2020) we included 180 SARS-CoV-2 positive cases: 127 HCWs (91 HCWcovid, 36 HCWoutbreak) and 53 patients. The attack rates ranged from 10-19% for patients, and 21% for HCWs. We estimated that there were 16 importation events (3 patients, 13 HCWs) that jointly led to 16 secondary cases. Most patient-to-patient transmission events involved patients having shared a ward (97.6%, 95% credible interval [CrI] 90.4-100%), in contrast to those having shared a room (44.4%, 95%CrI 27.8-62.5%). Transmission events tended to cluster by type of case: patientnoso were almost twice as likely to be infected by other patientnoso than expected (observed:expected ratio 1.91, 95%CrI 1.08 - 4.00, p = 0.02); similarly, HCWoutbreak were more than twice as likely to be infected by other HCWoutbreak than expected (2.25, 95%CrI 1.00-8.00, p = 0.04). The proportion of infectors of HCWcovid were as expected as random. The proportions of high transmitters ([≥]2 secondary cases) were significantly higher among HCWoutbreak than patientnoso in the late phases (26.2% vs. 13.4%, p<2.2e-16) of the outbreak. ConclusionsMost importation events were linked to HCW. Unexpectedly, transmission between HCWcovid was more limited than transmission between patients and HCWoutbreak. This highlights gaps in infection control and suggests possible areas of improvements to limit the extent of nosocomial transmission.

A novel spectrofluorimetric method for determination of lomefloxacin adopting on zinc(II) chelation strategy: Application in human plasma.

A new sensitive and instantaneous spectrofluorimetric method for efficient determination of lomefloxacin (LMX) in its pure, dosage form and human plasma was designed. The developed method depends on formation of a metal-chelation compound of LMX as a ligand with zinc(II) in a buffer of acetate (pH 5.5). The following parameters; type of metal, concentration of metal, pH, type of buffer and diluting solvent were optimized. After carefully investigation; 0.2 mM zinc, 2.0 ml acetate buffer (pH 5.5) and water as diluting solvent were set as optimum reaction conditions. Under these conditions, a large increase in the intensity of the fluorescence of LMX was attained at 450 after excitation at 284 nm. The limits of detection and quantification were 5.8 and 1.9 ng ml-1 , respectively, with linearity range of 10.0 to 500.0 ng ml-1 . The binding mode of LMX and zinc(II) ion (Zn2+ ) was found to be 2:1, respectively, and confirmed by Job's plot method. Furthermore, it extended to the analysis of LMX in the spiked plasma of humans with percentage recovery (98.70 ± 0.97 to 100.30 ± 1.69%, n = 3).

Development and Characterization of Eudragit-RL-100-Based Aceclofenac Sustained-Release Matrix Pellets Prepared via Extrusion/Spheronization.

Aceclofenac (AC) is a nonsteroidal anti-inflammatory drug used in the treatment of chronic pain in conditions such as rheumatoid arthritis, with frequent administration during the day. The formulation of sustained release matrix pellets can provide a promising alternative dosage form that controls the release of the drug, with less blood fluctuation and side effects-especially those related to the gastric system. The extrusion/spheronization technique was used to formulate AC matrix pellets. The response surface methodology (version 17.2.02.; Statgraphics Centurion) was used to study the impacts of Eudragit RL 100 and PVP K90 binder solution concentrations on the pellets' wet mass peak torque, pellet size, and the release of the drug. Statistically, a significant synergistic effect of PVP K90 concentration on the peak torque and pellet size was observed (p = 0.0156 and 0.031, respectively), while Eudragit RL 100 showed significant antagonistic effects (p = 0.042 and 0.013, respectively). The peak torque decreased from 0.513 ± 0.022 to 0.41 ± 0.021 when increasing the Eudragit RL 100 from 0 to 20%, and the pellet size decreased from 0.914 ± 0.047 to 0.789 ± 0.074 nm. The tested independent factors did not significantly affect the drug release in the acidic medium within 2 h, but these pellet formulae maintained the drug release at less than 10% in the acidic medium (pH 1.2), which may decrease gastric irritation side effects. In contrast, a highly significant synergistic effect of Eudragit and highly antagonistic effect of the PVP solution on drug release in the alkaline-pH medium were observed (p = 0.002 and 0.007, respectively). The optimized pellet formula derived from the statistical program, composed of 3.21% Eudragit and 5% PVP solution, showed peak torque of 0.861 ± 0.056 Nm and pellet size of 1090 ± 85 µm, and resulted in a significant retardation effect on the release after 8 h compared to the untreated drug.

Occupational versus community risk of SARS-CoV-2 infection among employees of a long-term care facility: an observational study

ObjectivesWe investigated the relative contribution of occupational (vs. community) exposure for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among employees of a university-affiliated long-term care facility (LTCF), during the 1st pandemic wave in Switzerland (March to June 2020). MethodsWe performed a nested analysis of a seroprevalence study among all volunteering LTCF staff to determine community and nosocomial risk factors for SARS-CoV-2 seropositivity using modified Poison regression. We also combined epidemiological and genetic sequencing data from a coronavirus disease 2019 (COVID-19) outbreak investigation in a LTCF ward to infer transmission dynamics and acquisition routes of SARS-CoV-2, and evaluated strain relatedness using a maximum likelihood phylogenetic tree. ResultsAmong 285 LTCF employees, 176 participated in the seroprevalence study, of whom 30 (17%) were seropositive for SARS-CoV-2. Most (141/176, 80%) were healthcare workers (HCWs). Risk factors for seropositivity included exposure to a COVID-19 inpatient (adjusted prevalence ratio [aPR] 2.6; 95%CI 0.9-8.1) and community contact with a COVID-19 case (aPR 1.7; 95%CI 0.8-3.5). Among 18 employees included in the outbreak investigation, the outbreak reconstruction suggests 4 likely importation events by HCWs with secondary transmissions to other HCWs and patients. ConclusionsThese two complementary epidemiologic and molecular approaches suggest a substantial contribution of both occupational and community exposures to COVID-19 risk among HCWs in LTCFs. These data may help to better assess the importance of occupational health hazards and related legal implications during the COVID-19 pandemic.

Predicting hospital-onset COVID-19 infections using dynamic networks of patient contacts: an observational study

BackgroundReal-time prediction is key to prevention and control of healthcare-associated infections. Contacts between individuals drive infections, yet most prediction frameworks fail to capture the dynamics of contact. We develop a real-time machine learning framework that incorporates dynamic patient contact networks to predict patient-level hospital-onset COVID-19 infections (HOCIs), which we test and validate on international multi-site datasets spanning epidemic and endemic periods. MethodsOur framework extracts dynamic contact networks from routinely collected hospital data and combines them with patient clinical attributes and background contextual hospital data to forecast the infection status of individual patients. We train and test the HOCI prediction framework using 51,157 hospital patients admitted to a UK (London) National Health Service (NHS) Trust from 01 April 2020 to 01 April 2021, spanning UK COVID-19 surges 1 and 2. We then validate the framework by applying it to data from a non-UK (Geneva) hospital site during an epidemic surge (40,057 total inpatients) and to data from the same London Trust from a subsequent period post surge 2, when COVID-19 had become endemic (43,375 total inpatients). FindingsBased on the training data (London data spanning surges 1 and 2), the framework achieved high predictive performance using all variables (AUC-ROC 0{middle dot}89 [0{middle dot}88-0{middle dot}90]) but was almost as predictive using only contact network variables (AUC-ROC 0{middle dot}88 [0{middle dot}86-0{middle dot}90]), and more so than using only hospital contextual (AUC-ROC 0{middle dot}82 [0{middle dot}80-0{middle dot}84]) or patient clinical (AUC-ROC 0{middle dot}64 [0{middle dot}62-0{middle dot}66]) variables. The top three risk factors we identified consisted of one hospital contextual variable (background hospital COVID-19 prevalence) and two contact network variables (network closeness, and number of direct contacts to infectious patients), and together achieved AUC-ROC 0{middle dot}85 [0{middle dot}82-0{middle dot}88]. Furthermore, the addition of contact network variables improved performance relative to hospital contextual variables on both the non-UK (AUC-ROC increased from 0{middle dot}84 [0{middle dot}82-0{middle dot}86] to 0{middle dot}88 [0{middle dot}86-0{middle dot}90]) and the UK validation datasets (AUC-ROC increased from 0{middle dot}52 [0{middle dot}49-0{middle dot}53] to 0{middle dot}68 [0{middle dot}64-0{middle dot}70]). InterpretationOur results suggest that dynamic patient contact networks can be a robust predictor of respiratory viral infections spreading in hospitals. Their integration in clinical care has the potential to enhance individualised infection prevention and early diagnosis. FundingMedical Research Foundation, World Health Organisation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Swiss National Science Foundation, German Research Foundation.

Massive Gastrointestinal Haemorrhage Unusual Presentation of Gastrointestinal Stromal Tumors of the Jejunum: Case Report and Literature Review.

Although gastrointestinal stromal tumors (GISTs) are rare tumors, they are the most common tumors of mesenchymal origin of the gastrointestinal tract. GISTs present with nonspecific clinical manifestation and they are discovered incidentally during endoscopic or radiological investigations. Massive life-threatening bleeding that requires urgent surgery is rare. We present a case of small bowel GIST that presented with massive lower gastrointestinal bleeding that required urgent surgical intervention.