Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: a multicenter cohort study.

BACKGROUND: Inhaled nitric oxide (iNO) is used as rescue therapy in patients with refractory hypoxemia due to severe COVID-19 acute respiratory distress syndrome (ARDS) despite the recommendation against the use of this treatment. To date, the effect of iNO on the clinical outcomes of critically ill COVID-19 patients with moderate-to-severe ARDS remains arguable. Therefore, this study aimed to evaluate the use of iNO in critically ill COVID-19 patients with moderate-to-severe ARDS. METHODS: This multicenter, retrospective cohort study included critically ill adult patients with confirmed COVID-19 treated from March 01, 2020, until July 31, 2021. Eligible patients with moderate-to-severe ARDS were subsequently categorized into two groups based on inhaled nitric oxide (iNO) use throughout their ICU stay. The primary endpoint was the improvement in oxygenation parameters 24 h after iNO use. Other outcomes were considered secondary. Propensity score matching (1:2) was used based on the predefined criteria. RESULTS: A total of 1598 patients were screened, and 815 were included based on the eligibility criteria. Among them, 210 patients were matched based on predefined criteria. Oxygenation parameters (PaO2, FiO2 requirement, P/F ratio, oxygenation index) were significantly improved 24 h after iNO administration within a median of six days of ICU admission. However, the risk of 30-day and in-hospital mortality were found to be similar between the two groups (HR: 1.18; 95% CI: 0.77, 1.82; p = 0.45 and HR: 1.40; 95% CI: 0.94, 2.11; p= 0.10, respectively). On the other hand, ventilator-free days (VFDs) were significantly fewer, and  ICU and hospital LOS were significantly longer in the iNO group. In addition, patients who received iNO had higher odds of acute kidney injury (AKI) (OR (95% CI): 2.35 (1.30, 4.26), p value = 0.005) and hospital/ventilator-acquired pneumonia (OR (95% CI): 3.2 (1.76, 5.83), p value = 0.001). CONCLUSION: In critically ill COVID-19 patients with moderate-to-severe ARDS, iNO rescue therapy is associated with improved oxygenation parameters but no mortality benefits. Moreover, iNO use is associated with higher odds of AKI, pneumonia, longer LOS, and fewer VFDs.

The Role of Inhaled Corticosteroids (ICS) in Critically Ill Patients With COVID-19: A Multicenter, Cohort Study.

Background: Severe coronavirus disease 2019 (COVID-19) can boost the systematic inflammatory response in critically ill patients, causing a systemic hyperinflammatory state leading to multiple complications. In COVID-19 patients, the use of inhaled corticosteroids (ICS) is surrounded by controversy regarding their impacts on viral infections. This study aims to evaluate the safety and efficacy of ICS in critically ill patients with COVID-19 and its clinical outcomes. Method: A multicenter, noninterventional, cohort study for critically ill patients with COVID-19 who received ICS. All patients aged ≥ 18 years old with confirmed COVID-19 and admitted to intensive care units (ICUs) between March 1, 2020 and March 31, 2021 were screened. Eligible patients were classified into two groups based on the use of ICS ± long-acting beta-agonists (LABA) during ICU stay. Propensity score (PS)-matched was used based on patient's Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, systemic corticosteroids use, and acute kidney injury (AKI) within 24 h of ICU admission. We considered a P-value of < 0.05 statistically significant. Results: A total of 954 patients were eligible; 130 patients were included after PS matching (1:1 ratio). The 30-day mortality (hazard ratio [HR] [95% confidence interval [CI]]: 0.53 [0.31, 0.93], P-value = 0.03) was statistically significant lower in patients who received ICS. Conversely, the in-hospital mortality, ventilator-free days (VFDs), ICU length of stay (LOS), and hospital LOS were not statistically significant between the two groups. Conclusion: The use of ICS ± LABA in COVID-19 patients may have survival benefits at 30 days. However, it was not associated with in-hospital mortality benefits nor VFDs.

Rising prevalence of multiple sclerosis in Saudi Arabia, a descriptive study.

BACKGROUND: In 2015, the first nationwide, multicenter Multiple Sclerosis (MS) registry was initiated in the Kingdom of Saudi Arabia (KSA) mainly with an objective to describe current epidemiology, disease patterns, and clinical characteristics of MS in Saudi Arabia. This article aimed to report initial findings of the registry and regional prevalence of MS. METHOD: In 2015, a national MS registry was launched in KSA to register all MS patient with confirmed diagnosis according to the 2010 McDonald Criteria. The registry aimed to identify and recruit all healthcare facilities treating MS patients in the Kingdom, and collect data such as demographics, clinical characteristics (disease onset, diagnosis, presentation of symptoms at onset, disease course, relapse rate, and disability measures), family history, and treatments. All the included sites have obtained IRB/EC approvals for participating in the registry. Currently, the registry includes 20 hospitals from different regions across the Kingdom. The Projected prevalence was calculated based on the assumption that the number of diagnosed MS cases in participating hospitals (in each region) is similar to the number of cases in remaining nonparticipant hospitals in the same region. RESULTS: As of September 2018, the registry has included 20 hospitals from the different regions across the Kingdom and has collected comprehensive data on 2516 patients from those hospitals, with median age 32 (Range: 11-63) and 66.5% being females. The reported prevalence of MS for those hospitals was estimated to be 7.70/100,000 population and 11.80/100,000 Saudi nationals. Based on the assumption made earlier, we projected the prevalence for each region and for the country as a whole. The overall prevalence of MS at the country level was reported to be 40.40/100,000 total population and 61.95/100,000 Saudi nationals. Around 3 out of every 4 patients (77.5%) were 40 years of age or younger. Female to male ratio was 2:1. The prevalence was higher among females, young and educated individuals across all five regions of Saudi Arabia. CONCLUSION: The prevalence of MS has significantly increased in Saudi Arabia but is still much lower than that in the western and other neighboring countries like Kuwait, Qatar, and the UAE. However, compared to the past rates, Saudi Arabia's projected prevalence of MS through this national study is 40.40/100,000 population, putting the Kingdom above the low risk zone as per Kurtzke classification. The projected prevalence was estimated to be much higher among Saudi nationals (61.95/100,000 Saudi-nationals). The prevalence was higher among female, younger and educated individuals. Further studies are needed to assess the risk factors associated with increased prevalence in Saudi Arabia.

Correlation of optical coherence tomography and histology in microcystic adnexal carcinoma: a case report.

BACKGROUND/AIMS: Herein, we report a case of microcystic adnexal carcinoma (MAC), which we correlated and evaluated by optical coherence tomography (OCT) and conventional H&E histology. METHODS: A commercially available OCT scanner was used for imaging. Several multi-slice images were obtained from the central portion of the lesion. Correlation of OCT findings with histology was performed retrospectively. RESULTS: Microcystic adnexal carcinoma showed characteristic criteria, which were divided into superficial and sub-epidermal findings. CONCLUSION: The use of OCT can visualize characteristic criteria of MAC, thus enabling prompt diagnosis before surgery.

Assessment of a scoring system for Basal Cell Carcinoma with multi-beam optical coherence tomography.

BACKGROUND: Multi-beam optical coherence tomography (OCT) is a novel method of non-invasive skin imaging allowing the evaluation of tissue at high level of lateral and axial resolution. It permits the horizontal and vertical evaluation of the extent of diseases. OBJECTIVE: Herein, we aimed to validate diagnosing basal cell carcinoma (BCC) by OCT using a newly developed scoring system ('Berlin Score'-BS). This was based on the predetermined criteria such as dark border underneath the tumour and ovoid structures. Their frequency and distribution in subtypes of BCC were evaluated. METHODS: The study was conducted in two phases, in which the experience of examiner differed. A total of 127 BCC and 50 other skin diseases were examined. In phase one, students performed the evaluation of skin lesions using the BS, while in phase two an expert performed the scoring in a different subset of patients. RESULTS: Application of BS by students revealed sensitivity and specificity of 92.8% (95% CI 85.4-96.8) and 24.1% (95% CI 11.0-43.4) when reaching the lower threshold BS≥8. The most common BCC subtypes were superficial (28.7%) and nodular (22.6%) BCC. Second phase was carried out to verify collected data by a dermatological specialist and expert in using OCT. Increased sensitivity and specificity for OCT amounted to 96.6% (95% CI 80.4-99.8) and 75.2% (95% CI 52.5-90.9). Thereby 88% of all diagnoses were correctly classified confirmed by histopathology. CONCLUSION: Multi-beam optical coherence tomography revealed to be a fast and promising device for assessing lesions by means of BS. Both students, who benefit from practice in handling OCT, and experts are able to perform this procedure. However, experience and training in the interpretation markedly increased sensitivity and specificity of the BS in our study. Moreover, redefinition and refining of the criteria seems necessary and may further increase the diagnostic value of OCT for NMSC.

Doxycycline's Potential Role in Reducing Thrombosis and Mortality in Critically Ill Patients With COVID-19: A Multicenter Cohort Study.

Doxycycline has revealed potential effects in animal studies to prevent thrombosis and reduce mortality. However, less is known about its antithrombotic role in patients with COVID-19. Our study aimed to evaluate doxycycline's impact on clinical outcomes in critically ill patients with COVID-19. A multicenter retrospective cohort study was conducted between March 1, 2020, and July 31, 2021. Patients who received doxycycline in intensive care units (ICUs) were compared to patients who did not (control). The primary outcome was the composite thrombotic events. The secondary outcomes were 30-day and in-hospital mortality, length of stay, ventilator-free days, and complications during ICU stay. Propensity score (PS) matching was used based on the selected criteria. Logistic, negative binomial, and Cox proportional hazards regression analyses were used as appropriate. After PS (1:3) matching, 664 patients (doxycycline n = 166, control n = 498) were included. The number of thromboembolic events was lower in the doxycycline group (OR: 0.54; 95% CI: 0.26-1.08; P = .08); however, it failed to reach to a statistical significance. Moreover, D-dimer levels and 30-day mortality were lower in the doxycycline group (beta coefficient [95% CI]: -0.22 [-0.46, 0.03; P = .08]; HR: 0.73; 95% CI: 0.52-1.00; P = .05, respectively). In addition, patients who received doxycycline had significantly lower odds of bacterial/fungal pneumonia (OR: 0.65; 95% CI: 0.44-0.94; P = .02). The use of doxycycline as adjunctive therapy in critically ill patients with COVID-19 might may be a desirable therapeutic option for thrombosis reduction and survival benefits.

The impact of HMG-CoA reductase inhibitors use on the clinical outcomes in critically ill patients with COVID-19: A multicenter, cohort study.

Background: The cardiovascular complications of Coronavirus Disease 2019 (COVID-19) may be attributed to the hyperinflammatory state leading to increased mortality in patients with COVID-19. HMG-CoA Reductase Inhibitors (statins) are known to have pleiotropic and anti-inflammatory effects and may have antiviral activity along with their cholesterol-lowering activity. Thus, statin therapy is potentially a potent adjuvant therapy in COVID-19 infection. This study investigated the impact of statin use on the clinical outcome of critically ill patients with COVID-19. Methods: A multicenter, retrospective cohort study of all adult critically ill patients with confirmed COVID-19 who were admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on the statin use during ICU stay and were matched with a propensity score based on patient's age and admission APACHE II and SOFA scores. The primary endpoint was in-hospital mortality, while 30 day mortality, ventilator-free days (VFDs) at 30 days, and ICU complications were secondary endpoints. Results: A total of 1,049 patients were eligible; 502 patients were included after propensity score matching (1:1 ratio). The in-hospital mortality [hazard ratio 0.69 (95% CI 0.54, 0.89), P = 0.004] and 30-day mortality [hazard ratio 0.75 (95% CI 0.58, 0.98), P = 0.03] were significantly lower in patients who received statin therapy on multivariable cox proportional hazards regression analysis. Moreover, patients who received statin therapy had lower odds of hospital-acquired pneumonia [OR 0.48 (95% CI 0.32, 0.69), P < 0.001], lower levels of inflammatory markers on follow-up, and no increased risk of liver injury. Conclusion: The use of statin therapy during ICU stay in critically ill patients with COVID-19 may have a beneficial role and survival benefit with a good safety profile.

Clinical features and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19): A multicenter cohort study.

BACKGROUND: Coronavirus disease-19 (COVID-19) manifested by a broad spectrum of symptoms, ranging from asymptomatic manifestations to severe illness and death. The purpose of the study was to extensively describe the clinical features and outcomes in critically ill patients with COVID-19 in Saudi Arabia. METHOD: This was a multicenter, non-interventional cohort study for all critically ill patients aged 18 years or older, admitted to intensive care units (ICUs) between March 1 to August 31, 2020, with an objectively confirmed diagnosis of COVID-19. The diagnosis of COVID-19 was confirmed by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on nasopharyngeal and/or throat swabs. Multivariate logistic regression and generalized linear regression were used. We considered a P value of <0.05 statistically significant. RESULTS: A total of 560 patients met the inclusion criteria. An extensive list of clinical features was associated with higher 30-day ICU mortality rates, such as requiring mechanical ventilation (MV) or developing acute kidney injury within 24 hours of ICU admission, higher body temperature, white blood cells, blood glucose level, serum creatinine, fibrinogen, procalcitonin, creatine phosphokinase, aspartate aminotransferase, and total iron-binding capacity. During ICU stay, the most common complication was respiratory failure that required MV (71.4%), followed by acute kidney injury (AKI) and thrombosis with a proportion of 46.8% and 11.4%, respectively. CONCLUSION: Among patients with COVID-19 who were admitted to the ICU, several variables were associated with an increased risk of ICU mortality at 30 days. Respiratory failure that required MV, AKI, and thrombosis were the most common complications during ICU stay.

Late presentation of abdominal aortic occlusion in a patient with spinal cord injury.

Although pressure ulcers are a common problem in patients with paraplegia, pressure is not the only cause of them. This case report illustrates that distal abdominal aortic obstruction resulted in multiple ulcers in a paraplegic patient.

[Research Assessment in Plastic and Reconstructive Surgery on a National Level: A 5-Years Systematic Review of Research Activity in German University Hospitals]. / Eine Analyse der Forschungsaktivität universitärer Kliniken für Plastische Chirurgie im nationalen Vergleich: Eine systematische 5-Jahres Evaluation der Forschungsaktivität in Deutschland.

BACKGROUND: In plastic surgery, a broad spectrum of research activity has been performed over the past decade. However, compared with other medical fields, there seems to be a lack of central coordination in the individual research areas. Also no comprehensive, periodical assessment has been undertaken to date. This study aims to provide an overview of German research activity in plastic surgery departments affiliated to medical universities. METHODS: We performed a 5-year interval (01/2010-12/2014) survey of PubMed-listed publications of plastic surgery departments in German university hospitals. For each university (n=11), statistical analyses of the following parameters were performed: distribution of research fields, number of publications, annual cumulative impact sum (IS) and impact factor (IF). RESULTS: For the above-mentioned period, a total of n=904 publications were analysed. Ranking among academic departments was as follows: number of publications: 1. Medizinische Hochschule Hannover 178 (annual average x̅=36/median x͂=34; 2. University Hospital of Erlangen 115 (x̅=23/x͂=23); 3. Bergmannsheil Bochum 90 (x̅=18/x͂=19). The annual impact sum (IS) averaged 33.51 (SD 11.088, p<0.05); separated IS: 1. Medizinische Hochschule Hannover x̅=74.66, x͂=62.22, 2. University Hospital of Erlangen x̅=53.24, x͂=50.84, 3. University Hospital RWTH Aachen x̅=46.12, x͂=44.67. The average impact factor per publication was: 1.98 (SD 0.31, p<0.05); separated IF: 1. University Hospital RWTH Aachen x̅=2.76, x͂=2.79; 2. University Hospital of Erlangen x̅=2.34, x͂=2.46; 3. Medizinische Hochschule Hannover x̅=2.08, x͂=2.05. The analysed publications were distributed as follows: 43% reviews, 20% cell biology/tissue engineering, 10% reconstruction, 27% others (including wound healing, vessel/nerve research, hand surgery, burn, aesthetics, oncology). CONCLUSION: Based on this comprehensive analysis, it seems that a periodical assessment of current research activity would be useful for the future. Data assessments should be started on European and international levels and should also be applied to other surgical and medical disciplines.

Osteogenesis imperfecta: evidence for the existence of an abnormal amino acid sequence in the molecule of dermal collagen.

A collagen-type pattern of peptide and amino acid spots was obtained when partial hydrolysates of normal human dermis were examined by a specially developed thin-layer chromatographic (TLC) 'finger-printing' technique. The pattern was consistent and independent of age and sex. Two clinically similar cases of osteogenesis imperfecta congenita gave identical patterns which differed in specific regions from those given by their age-matched, normal controls. A single case of osteogenesis imperfecta tarda showed the same overall pattern as the congenita cases. It is concluded that an abnormal amino acid sequence occurs in the collagen molecule of both types of osteogenesis imperfecta.

Improved technique for the analysis of amino acids and related compounds on thin layers of cellulose.XI. Direct, visual micro-method for investigating the primary structural sequence of collagen and other proteins.

The present paper describes a new variation of the "finger printing" technique for examining the primary structure of proteins. It is based on the production of a reproducible, partial acid hydrolysate consisting of amino acids and small peptides which are separated into compact spots by bi-dimensional thin-layer chromatography. The spots are characterized by ther Rf values and colour reactions with a variety of reagents. The method was initially developed for collagen but has been applied to other proteins, with interesting results. It has developed logically from earlier, systematic studies on amino acids and peptides, and holds promise for the comparative investigation of normal and diseased human collagen.