The Pathogenesis of Pierre Robin Sequence through a Review of SOX9 and Its Interactions.

The literature does not offer any review of the pathogenesis of the clinical features of syndromes with Pierre Robin sequence (PRS). The senior author (MMA) proposed a hypothesis that SOX9 and its interactions may play a key role in this pathogenesis. The current review aims to test this hypothesis. Methods: Three literature searches were made: the first aimed to document the main syndromes associated with PRS; and the second was to document the main functions of SOX9 in development; and the third was to investigate if SOX9 and its interactions may play a role in the pathogenesis. Results: SOX9 is the main positive regulator in the development of the mandibular cartilage and it also enhances collagen type II (the main collagen type in cartilage) expression in the mandibular cartilage. Furthermore, SOX9 participates in neural crest development, binds to the exon junction complex, and participates in sex determination. The interactions of SOX9 could explain the pathogenesis of the clinical features of syndromic PRS. These included interactions with collagen type II (in Strickler syndrome), exon junction complex (in Richier-Costa-Periera syndrome), glucose (in Catel-Manzke syndrome), RNA-binding proteins (in TARP syndrome), and the spliceosome (in cerebra-costo-mandibular syndrome). Finally, SOX9 mutations cause campomelic dysplasia. Conclusions: The review supports the hypothesis of the participation of SOX9 in the pathogenesis of the clinical features of syndromic and nonsyndromic PRS. This should guide future research on the topic.

Risk of COVID-19 in healthcare workers working in intensive care setting.

BACKGROUND: The higher risk of COVID-19 in health care workers (HCWs) is well-known. However, the risk within HCWs is not fully understood. The objective was to compare the COVID-19 risk in intensive care unit (ICU) vs non-ICU locations. METHODS: A prospective surveillance study was conducted among HCWs at a large tertiary care facility in Riyadh between March 1st to November 30th, 2020. HCWs included both clinical (provide direct patient care) and nonclinical positions (do not provide direct patient care). RESULTS: A total 1,594 HCWs with COVID-19 were included; 103 (6.5%) working in ICU and 1,491 (93.5%) working in non-ICU locations. Compared with non-ICU locations, ICU had more nurses (54.4% vs 22.1%, P < .001) and less support staff (2.9% vs 53.1%, P < .001). COVID-19 infection was similar in ICU and non-ICU locations (9.0% vs 9.8%, P = .374). However, it was significantly higher in ICU nurses (12.3% vs 6.5%, P < .001). Support staff had higher risk than other HCWs, irrespective of ICU working status (15.1% vs 7.2%, P < 0.001). The crude relative risk of COVID-19 in ICU vs non-ICU locations was 0.92, 95% confidence interval ( was 0.76-1.11 (P = .374). However, relative risk adjusted for professional category was significantly increased to 1.23, 95% confidence interval 1.01-1.50 (P = .036). CONCLUSIONS: ICU had a significantly higher risk of COVID-19 infection only after adjusting for the distribution and risk of different professional categories. The latter is probably determined by both exposure level and protection practices. The finding underscores the importance of strict implementation of preventive measures among all HCWs, including those performing nonclinical services.

Post-vaccination SARS-CoV-2 infection among healthcare workers in tertiary care hospitals in Saudi Arabia: A case series.

Healthcare workers have been categorized among the priority groups for COVID-19 vaccination. However, post-vaccination infections have been identified. This study was conducted to investigate SARS-CoV-2 infection among healthcare workers (HCWs) who received the COVID-19 vaccine. A case series in a multicenter healthcare system in Saudi Arabia was created from HCWs who had (PCR-RT) confirmed SARS-CoV-2 infection after at least one dose of Pfizer-BioNTech vaccination. A total of 20 healthcare workers (HCWs) have been included. The majority (70.0%) were males and the average age was 39.4 ± 10.1 years. They included physicians (55.0%), nurses (25.0%) and other HCWs (20.0%). Eighteen (90%) HCWs had infection after the first dose; 47.1% within the first week, 41.2% within the second week, and 11.8% within the third week. Only two HCWs (10.0%) had infection one week after the second dose. The majority (63.2%) had mild (52.6%) or moderate (10.3%) disease with no severe disease or hospitalization. The majority of post-vaccination COVID-19 infections among HCWs occurred before the full protection of the vaccine is gained. Suspicion of COVID-19 infection should be considered even with a history of COVID-19 vaccination. Recently vaccinated HCWs should be advised to fully comply with all recommended precautions to prevent COVID-19 transmission.

Type II D Phalangeal Neck Fractures in Children: A Series of 20 Cases Treated According to a Preset Stepwise Algorithm.

Introduction Type II phalangeal neck fractures are defined as displaced fractures with bone-to-bone contact at the fracture site. In the type II D subtype, the distal fracture fragment is thin. A review of the literature did not reveal any study investigating the outcome of management of these fractures. Patients and Methods This is a retrospective study of 20 consecutive children with type II D phalangeal neck fractures treated over the past 4 years. Demographic data were reviewed. All cases were managed according to the preset stepwise algorithm. The outcome of management at final follow-up was documented using Al-Qattan's grading system. Results The mean age was 30 months (range 12-80 months). There were 12 males and 8 females. The mean follow-up was 2 years (range 7 months to 3 years). The largest two categories within the management algorithm were patients with minimally displaced fractures treated conservatively ( n = 8) and those with displaced fractures treated with closed reduction and percutaneous K-wire fixation ( n = 9). Fischer exact test was used to compare the outcome in these two groups and the p value was significant ( p = 0.015), indicating a significantly better outcome in the former group. Conclusion Several conclusions were made from the study. Type II D of phalangeal neck fractures tend to occur in young children and the majority involve the middle phalanx. The thinness of the distal fracture fragment makes standard techniques of closed reduction more difficult. However, flexion of the proximal and distal joints appears to be effective in reducing dorsally displaced type II D fractures by closed means. Finally, a more conservative approach to minimally displaced type II D fractures results in a better outcome compared with closed reduction and percutaneous K-wire fixation.

Risk of COVID-19 morbidity and mortality among healthcare workers working in a Large Tertiary Care Hospital.

OBJECTIVES: To estimate COVID-19 infection and outcomes among healthcare workers (HCWs) compared with non-HCWs. METHODS: A prospective surveillance study was conducted among HCWs and non-HCWs eligible for treatment at a large tertiary care facility in Riyadh between March 1st to November 30th, 2020. RESULTS: A total 13,219 cases with confirmed COVID-19 have been detected during the study; 1596 (12.1%) HCW patients (HCWPs) and 11623 (87.9%) non-HCWPs. Infection per 100 population was almost ten-fold higher in HCWs compared with non-HCWs (9.78 versus 1.01, p<0.001). The risk of infection in support staff (15.1%) was almost double the risk in other professional groups (p<0.001). Hospitalization (14.1% versus 1.8%, p<0.001), ICU admission (3.0% versus 0.5%, p<0.001), and case fatality (0.13% versus 2.77%, p<0.001) were significantly lower in HCWPs compared with non-HCWPs. The mortality per 100,000 population was significantly lower in HCWs compared with non-HCWs (12.3 and 28.1, p<0.001). CONCLUSION: HCWs are at ten-fold higher risk of COVID-19 infection but have much better outcomes compared with non-HCWs. More strict infection control measures are still required to protect HCWs, including those who are not involved in direct patient care.

High Burden of Resistant Gram Negative Pathogens Causing Device-associated Healthcare Infections in a Tertiary Care Setting in Saudi Arabia, 2008-2016.

OBJECTIVES: There is local and regional deficiency in the data examining the contribution of resistant pathogens to device-associated healthcare-associated infections (DA-HAIs). The objective was to examine such data in a multi-hospital system in Saudi Arabia in comparison with the US National Health Surveillance Network (NHSN). METHODS: Surveillance of DA-HAIs was prospectively conducted between 2008 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Consecutive NHSN reports were used for comparisons. Definitions and methodology of DA-HAIs and bacterial resistance were based on NHSN. RESULTS: A total 1260 pathogens causing 1141 DA-HAI events were included. Gram negative pathogens (GNPs) were responsible for 62.5% of DA-HAIs, with a significantly higher Klebsiella, Pseudomonas, Acinetobacter, and Enterobacter than NHSN hospitals. Approximately 28.3% of GNPs and 23.5% of gram positive pathogens (GPPs) had some type of resistance. Nearly 34.3% of Klebsiella were resistant to third/fourth generation cephalosporins, 4.8% of Enterobacteriaceae were carbapenem-resistant (CRE), 24.4% of Staphylococcus aureus were methicillin-resistant (MRSA), and 21.9% of Enterococci were vancomycin-resistant (VRE). Multidrug resistance (MDR) was 65.0% in Acinetobacter, 26.4% in Escherichia coli, 23.0% in Klebsiella, and 14.9% in Pseudomonas. Resistant GNPs including cephalosporin-resistant Klebsiella, MDR Klebsiella, and MDR Escherichia coli were significantly more frequent while resistant GPPs including MRSA and VRE were significantly less frequent than NHSN hospitals. CONCLUSION: The current findings showed heavier and more resistant contribution of GNPs to DA-HAIs in Saudi hospitals compared with American hospitals. The higher resistance rates in Klebsiella and Escherichia coli are alarming and call for effective antimicrobial stewardship programs.

High contribution and impact of resistant gram negative pathogens causing surgical site infections at a multi-hospital healthcare system in Saudi Arabia, 2007-2016.

BACKGROUND: Despite being largely preventable, surgical site infections (SSIs) are still one of the most frequent healthcare-associated infections. The presence of resistant pathogens can further augment their clinical and economic impacts. The objective was to estimate the distribution and resistance in SSI pathogens in Saudi Arabia and to compare them to the US National Healthcare Safety Network (NHSN) hospitals. METHODS: Targeted SSI surveillance was prospectively conducted on several surgical procedures done between 2007 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Definitions and methodology of SSI and bacterial resistance were based on NHSN. RESULTS: A total 492 pathogens causing 403 SSI events were included. The most frequent pathogens were Staphylococcus aureus (22.8%), Pseudomonas aeruginosa (20.1%), Klebsiella spp. (12.2%), and Escherichia coli (12.2%), with marked variability between surgeries. Approximately 30.3% of Staphylococcus aureus was methicillin-resistant (MRSA), 13.0% of Enterococcus spp. was vancomycin-resistant (VRE), and 5.5% of Enterobacteriaceae were carbapenem resistant (CRE). The highest multidrug-resistant (MDR) GNPs were Acinetobacter spp. (58.3%), Klebsiella spp. (20.4%) and Escherichia coli (16.3%). MRSA was significantly less frequent while cephalosporin-resistant Klebsiella spp., MDR Klebsiella spp., and MDR Escherichia coli were significantly more frequent in our hospitals compared with NHSN hospitals. CONCLUSION: GNPs in a tertiary care setting in Saudi Arabia are responsible for more than 60% of SSI with more resistant patterns than Western countries. This information may be critical to secure resources and ensure support for caregivers and healthcare leaders in implementing antimicrobial stewardship programs and evidence-based SSI preventive practices.

Ten-year resistance trends in pathogens causing healthcare-associated infections; reflection of infection control interventions at a multi-hospital healthcare system in Saudi Arabia, 2007-2016.

BACKGROUND: Studying temporal changes in resistant pathogens causing healthcare-associated infections (HAIs) is crucial in improving local antimicrobial and infection control practices. The objective was to describe ten-year trends of resistance in pathogens causing HAIs in a tertiary care setting in Saudi Arabia and to compare such trends with those of US National Health Surveillance Network (NHSN). METHODS: Pooled analysis of surveillance data that were prospectively collected between 2007 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Definitions and methodology of HAIs and antimicrobial resistance were based on NHSN. Consecutive NHSN reports were used for comparisons. RESULTS: A total 1544 pathogens causing 1531 HAI events were included. Gram negative pathogens (GNP) were responsible for 63% of HAIs, with a significant increasing trend in Klebsiella spp. and a decreasing trend in Acinetobacter. Methicillin-resistant Staphylococcus aureus (27.0%) was consistently less frequent than NHSN. Vancomycin-resistant Enterococci (VRE, 20.3%) were more than doubled during the study, closing the gap with NHSN. Carbapenem resistance was highest with Acinetobacter (68.3%) and Pseudomonas (36.8%). Increasing trends of carbapenem resistance were highest in Pseudomonas and Enterobacteriaceae, closing initial gaps with NHSN. With the exception of Klebsiella and Enterobacter, multidrug-resistant (MDR) GNPs were generally decreasing, mainly due to the decreasing resistance towards cephalosporins, fluoroquinolones, and aminoglycosides. CONCLUSION: The findings showed increasing trends of carbapenem resistance and VRE, which may reflect heavy use of carbapenems and vancomycin. These findings may highlight the need for effective antimicrobial stewardship programs, including monitoring and feedback on antimicrobial use and resistance.