Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis.

PURPOSE: To provide a precise summary and collate the hitherto available clinical evidence on the effect of vitamin D supplementation on clinical outcomes in COVID-19 patients. METHODS: PubMed/MEDLINE, Scopus, and Web of Science databases were systematically searched using appropriate keywords till June 8, 2021, to identify observational studies and randomized controlled trials (RCTs) reporting adverse clinical outcomes (ICU admission and/or mortality) in COVID-19 patients receiving vitamin D supplementation vs. those not receiving the same. Both prior use and use of vitamin D after COVID-19 diagnosis were considered. Unadjusted/adjusted pooled odds ratio (OR) with 95% confidence intervals (CI) were calculated (PROSPERO registration number CRD42021248488). RESULTS: We identified 13 studies (10 observational, 3 RCTs) pooling data retrieved from 2933 COVID-19 patients. Pooled analysis of unadjusted data showed that vitamin D use in COVID-19 was significantly associated with reduced ICU admission/mortality (OR 0.41, 95% CI: 0.20, 0.81, p = 0.01, I2 = 66%, random-effects model). Similarly, on pooling adjusted risk estimates, vitamin D was also found to reduce the risk of adverse outcomes (pooled OR 0.27, 95% CI: 0.08, 0.91, p = 0.03, I2 = 80%, random-effects model). Subgroup analysis showed that vitamin D supplementation was associated with improved clinical outcomes only in patients receiving the drug post-COVID-19 diagnosis and not in those who had received vitamin D before diagnosis. CONCLUSIONS: Vitamin D supplementation might be associated with improved clinical outcomes, especially when administered after the diagnosis of COVID-19. However, issues regarding the appropriate dose, duration, and mode of administration of vitamin D remain unanswered and need further research.

The influence of persistent bleeding after supracervical hysterectomy on depressive and anxious symptoms: a prospective bicenter study.

PURPOSE: Postoperative spotting is a frequent adverse symptom after laparoscopic supracervical hysterectomy (LSH). The conical excision (eLSH) reduces the postoperative spotting rate, but data in a larger collective are still rare and inconsistent. The influence of persistent bleeding on the anxious and depressive symptoms has not been analyzed yet. METHODS: 311 patients, who underwent a laparoscopic supracervical hysterectomy with conical excision (n = 163), or with straight cervical resection (n = 148) were included. Anxious and depressive symptoms and postoperative spotting were recorded before operation, at 3 month follow-up and at 1 year follow-up in both operative groups using a validated questionnaire (German version of Hospital Anxiety and Depression Scale, HADS-D) and additional questions concerning the frequency and impact of bleeding. Statistical analysis included the impairment of bleeding as well as its impact on depressive and anxious symptoms for both groups. RESULTS: 11.5% after eLSH and 15.5% after LSH reported spotting after 1 year. Supracervical hysterectomy significantly improves depressive and anxious symptoms at 3 and at 12 month follow-up for both groups (p < 0.001) independent on residual spotting. Patients with a preoperative continuous bleeding showed a maximum benefit independent on operative method. CONCLUSION: Laparoscopic supracervical hysterectomy has a positive effect on anxious and depressive symptoms in the short-term and intermediate-term follow-up. The conical excision of the cervical stump reduces postoperative spotting rate, but has no explicit advantage on symptoms of depression or anxiety, irrespective of residual postoperative spotting.

The influence of conventional and extended supracervical hysterectomy on sexuality and quality of life parameters: a prospective bi-center study with a special focus on postoperative spotting.

PURPOSE: Supracervical as well as total hysterectomy are considered to improve postoperative sexuality as well as quality of life, but the benefit of supracervical hysterectomy (LSH) is impaired in up to 20 percent by postoperative spotting. The aim of this study was to analyze the influence of a conical excision of the cervical stump during supracervical hysterectomy on the postoperative spotting rate and its influence on sexuality and in turn quality of life. METHODS: 321 Patients who underwent a laparoscopic supracervical hysterectomy with conical excision (extended laparoscopic supracervical hysterectomy, eLSH, n = 166, Dormagen hospital) or with straight cervical resection (laparoscopic supracervical hysterectomy, LSH, n = 133, MIC Clinics Berlin) were included. Sexual matters, quality of life parameters and additional questions were recorded before operation, at three months of follow up, and at one year of follow up in both groups using a validated questionnaire (German version of International Consultation on Incontinence Questionnaire Vaginal Symptoms Module, ICIQ_VS). Statistical analysis included the impact and impairment of bleeding on sexuality, quality of life in both groups and co-factors such as vaginal symptoms. RESULTS: 11.3% after eLSH and 15.5% after LSH reported spotting after 1 year. Supracervical hysterectomy significantly improves quality of life and sexuality and a conical excision of the remaining stump is associated with a lower but insignificantly reduced spotting rates. Postoperative spotting has no negative influence on sexual matter score of ICIQ_VS, but reduces the postoperative quality of life focusing on vaginal symptoms in a significant way. CONCLUSION: The improvement of ICIQ_VS scores after supracervical hysterectomy is independent of postoperative spotting, but the quality-of-life score is positively influenced by a reduction in the postoperative spotting rate.

Nonlocal Reaction-Diffusion Equations in Biomedical Applications.

Nonlocal reaction-diffusion equations describe various biological and biomedical applications. Their mathematical properties are essentially different in comparison with the local equations, and this difference can lead to important biological implications. This review will present the state of the art in the investigation of nonlocal reaction-diffusion models in biomedical applications. We will consider various models arising in mathematical immunology, neuroscience, cancer modelling, and we will discuss their mathematical properties, nonlinear dynamics, resulting spatiotemporal patterns and biological significance.

Fracture risk in hypoparathyroidism: a systematic review and meta-analysis.

In this meta-analysis, we analyzed 7 observational studies for assessing the fracture risk in patients with hypoparathyroidism (hypoPT). We found that the risk of vertebral fractures is increased by almost 2-fold, especially those with nonsurgical hypoPT. PURPOSE: Patients with hypoPT have higher bone mineral density than age- and sex-matched controls. This would theoretically translate into a lower risk of fractures, although available clinical evidence is contradictory. Hence, the present systematic review and meta-analysis was undertaken to collate and provide a precise summary of fracture risk in hypoPT. METHODS: PubMed, Scopus, and Web of Science databases were systematically searched using appropriate keywords till March 8, 2021, to identify observational studies reporting the rate of occurrence of fractures among hypoPT patients (nonsurgical and/or postsurgical) compared to non-hypoPT subjects (controls). Study quality was assessed using Newcastle-Ottawa Scale. Pooled odds ratio (OR) with 95% confidence intervals (CI) was calculated. Subgroup analyses of nonsurgical and postsurgical hypoPT patients were also conducted. RESULTS: We identified 7 observational studies of high-quality pooling data retrieved from 1470 patients with hypoPT. When stratified based on the skeletal site, pooled analyses showed that hypoPT patients were at an increased risk of vertebral fractures compared to non-hypoPT controls (OR 2.22, 95% CI: 1.23, 4.03, p = 0.009, I2 = 49%, random-effects model). The increased risk of vertebral fractures was seen only in patients with nonsurgical hypoPT (OR 2.31, 95% CI: 1.32, 4.03, p = 0.003, I2 = 3%, random-effects model) but not in those with postsurgical hypoPT. hypoPT patients were not at an increased or decreased risk of any, humerus, or proximal femur/hip fractures than controls. CONCLUSIONS: Nonsurgical hypoPT patients are at an almost 2-fold increased risk of vertebral fractures and thus need to be actively screened irrespective of the underlying BMD.

Assessment of DNA Methylation in p15, p16 and E-Cadherin Genes as a Screening Tool for Early Carcinoma Cervix.

Cancer cervix is diagnosed late in women due to anatomical inaccessibility of the area. Hence, a robust screening strategy will help detect carcinoma cervix early which will significantly decrease the mortality and morbidity due to this disease. We evaluated DNA methylation of three tumour suppressor genes p15, p16 and E-Cadherin on cervical smears to assess DNA methylation as a screening tool for detection of early cervical cancer in comparison to PAP smears. DNA was extracted from cervical smears of 20 cases and 30 controls. The DNA was bisulphite modified. Methylation specific PCR (MSP) was performed to assess the methylation status of the promoter region of each of the genes. MSP results were compared with PAP smears to assess the utility of DNA methylation of these genes in screening for cervical cancer. DNA methylation was detected in 55% subjects in p15 gene, 45% in p16 gene and 40% in E-Cadherin gene. This was statistically significant when compared to the controls. DNA methylation of E-Cadherin, and p15 genes as a panel has a sensitivity and specificity of 80% and 90% respectively, which is better than the sensitivity of PAP smear for detection of early cancer cervix. Increased DNA methylation is seen in p15, p16 and E-Cadherin genes in early cancer cervix. p15 and E-Cadherin in combination can be used as a screening tool for detection of early cancer cervix.

Endoscopic surgery: talent or training?

PURPOSE: There are two groups of undergraduate students involved in endoscopic surgery with different degrees of experience: average and more experience. This study proves whether the subjective impression of the laparoscopic trainer is verifiable and which factors influence extreme talent. METHODS: 21 medical students of the eighth term of the University of Witten-Herdecke participated in the study. On their first course day, students got instructed in suturing and knot technique. They were then required to tie a maximum of five knots within 2 h. After a week, students repeated this procedure. Time used for tying knots was stopped. RESULTS: Regarding the time students used for their first knots, great differences were provable (7-8 min, average 23 min). However, an adaption of the knotting time was noticed at the end of the first course day. This was confirmed during the second course day. Neither acquired factors (music, sport, etc.) nor individual factors (visual acuity, handedness, etc.) had any impact on the time used for knotting. Merely, one advantage was seen with the first knots with the factors of playing the guitar and having a more than 10-h surgical previous experience. Knotting times leveled off at 95% to less than 10 min, though. DISCUSSION: Neither normally talented nor extremely talented junior surgeons could be noticed, and so could not the co-factors providing an advantage or disadvantage for surgery, respectively. All prospective surgeons can learn defined tasks (knots) by short interval training, and thus show similarly good results after a few repetitions.

Social behavior-induced multistability in minimal competitive ecosystems.

Mimimal models of coordinated behavior of populations living in the same environment are introduced for the cases when they either both gain by mutual interactions, or one hunts the other one, or finally when they compete with each other. The equilibria of the systems are analysed, showing that in some cases the populations may both disappear. Coexistence leads to global asymptotic stability for symbiotic populations, or to Hopf bifurcations for predator-prey systems. Finally, a new very interesting phenomenon is discovered in the competition case: tristability may be achieved showing that the principle of competitive exclusion fails in this case. Indeed either one of the competing populations may thrive, but also the case of populations coexistence is allowed, for the same set of parameter values.

Analysis of a Prey-Predator Model with Non-local Interaction in the Prey Population.

Non-local reaction-diffusion equation is an important area to study the dynamics of the individuals which compete for resources. In this paper, we describe a prey-dependent predator-prey model with Holling type II functional response with a generalist predator. In particular, we want to see the behavior of the system in the presence of non-local interaction. Introduction of non-local intraspecific competition in prey population leads to some new characteristics in comparison with the local model. Comparisons have been made between the local and non-local interactions of the system. The range of non-local interaction enlarges the parametric domain on which stationary patterns exist. The periodic oscillation for the local model in the Hopf domain can be stabilized by suitable limit of strong non-local interaction. An increase in the range of non-local interaction increases the Turing domain up to a certain level, and then, it decreases. Also, increasing the range of non-local interaction results in the overlap of nearby foraging areas and hence alters the size of the localized patches and formation of multiple stationary patches. Numerical simulations have been carried out to validate the analytical findings and to establish the existence of multiple stationary patterns, oscillatory solution, two-periodic solution and other spatiotemporal dynamics.

Impact of GSTM1, GSTT1 and GSTP1 genes polymorphisms on clinical toxicities and response to concomitant chemoradiotherapy in cervical cancer.

BACKGROUND: Certain forms of chemoradiotherapy generate toxic reactive oxygen species, which may be ameliorated by antioxidant enzymes such as glutathione S-transferase (GST). Genetic polymorphisms of GST may predict treatment outcomes and can be used as genetic marker to screen patients before treatment. We hypothesised an effect of GST polymorphisms on the response and toxicities produced by chemoradiation therapy. MATERIALS AND METHODS: GST polymorphisms were determined by multiplex polymerase chain reaction and PCR-restriction fragment length polymorphism (PCR-RFLP) in 227 women with cervical cancer receiving cisplatin based chemoradiotherapy. Treatment response and toxicities were evaluated by standard internationally recognised criteria (RECIST and RTOG). RESULTS: Severe (grade 3-4) gastrointestinal and haematological toxicities were present in 22 (9.4%) and 16 (7.0%) patients, respectively. GSTM1 null, GSTT1 null and GSTP1 AG genotypes brought marginally better non-significant associations. In single locus analysis GSTP1 AG and GG was linked to greatest risk of severe (grade 3-4) gastrointestinal toxicity (OR = 3.12, P = 0.035 and OR = 6.99, P = 0.01, respectively). In gene-gene interaction analysis, GSTM1 null-GSTP1 GG showed 4.2-fold higher risk of severe gastrointestinal toxicity (P = 0.014). GSTT1 null-GSTP1 AG reached statistical significance with a 3.9-fold higher risk of high grade gastrointestinal toxicity (P = 0.038). CONCLUSIONS: Although no significant links were found between GST polymorphism and treatment response, null genotypes of GSTM1, GSTT1 and 'G' allele of GSTP1 bring a higher risk of severe gastrointestinal toxicity due to chemoradiation therapy in cervical cancer.

Role of pRIFLE Criteria in Early Diagnosis of Severity Staging of Neonatal AKI and its Impact on Management.

Mortality is high among sick neonates who have concomitant acute kidney injury (AKI). This observational study was done at Special Care Baby Unit (SCABU) of Dhaka Medical College Hospital (DMCH), Bangladesh from October 2013 to March 2014 to find out the role of pRIFLE criteria in prediction of severity stages of AKI in neonate and early intervention to see the immediate outcome. A total of 44 neonates with AKI were included, all were treated conservatively and with intermittent peritoneal dialysis (IPD) as needed. The neonate of ≤7 days old comprised the main bulk (n=28) and M: F = 21: 23. The diagnosis was based on eCCL criteria of pRIFLE showed that 40.9% neonates were at risk of AKI, 20.5% have had already injured. Higher proportions of neonates were classified as failure (38.6%). The distribution of biochemical parameters among three stages of AKI showed serum potassium was significantly higher in failure group (p<0.001). The serum creatinine both at baseline and at next evaluations were significantly raised in the failure group (p<0.001). However, failure group had a significantly longer hospital stay compared to risk and injury group (p<0.001). Multiorgan failure was found to be lower in the risk group compared to other two groups (p=0.026). Majority of the failure group needed dialysis as compared to the risk and injury group (p<0.001). The mortality was progressively higher from risk to failure groups (p=0.106). Overall 27% of the neonates diagnosed AKI by pRIFLE were died of the disease. The study concluded that pRIFLE staging in AKI is useful and sensitive in the diagnosis and management of AKI in neonates.

Long-term transients and complex dynamics of a stage-structured population with time delay and the Allee effect.

Traditionally, mathematical modeling in population ecology is mainly focused on asymptotic behavior of the model, i.e. as given by the system attractors. Recently, however, transient regimes and especially long-term transients have been recognized as playing a crucial role in the dynamics of ecosystems. In particular, long-term transients are a potential explanation of ecological regime shifts, when an apparently healthy population suddenly collapses and goes extinct. In this paper, we show that the interplay between delay in maturation and a strong Allee effect can result in long-term transients in a single species system. We first derive a simple 'conceptual' model of the population dynamics that incorporates both a strong Allee effect and maturation delay. Unlike much of the previous work, our approach is not empirical since our model is derived from basic principles. We show that the model exhibits a high complexity in its asymptotic dynamics including multi-periodic and chaotic attractors. We then show the existence of long-term transient dynamics in the system, when the population size oscillates for a long time between locally stable stationary states before it eventually settles either at the persistence equilibrium or goes extinct. The parametric space of the model is found to have a complex structure with the basins of attraction corresponding to the persistence and extinction states being of a complicated shape. This impedes the prediction of the eventual fate of the population, as a small variation in the maturation delay or the initial population size can either bring the population to extinction or ensure its persistence.

Prey-predator model with a nonlocal consumption of prey.

The prey-predator model with nonlocal consumption of prey introduced in this work extends previous studies of local reaction-diffusion models. Linear stability analysis of the homogeneous in space stationary solution and numerical simulations of nonhomogeneous solutions allow us to analyze bifurcations and dynamics of stationary solutions and of travelling waves. These solutions present some new properties in comparison with the local models. They correspond to different feeding strategies of predators observed in ecology.

Inter- and intraobserver reliability of the Rockwood classification in acute acromioclavicular joint dislocations.

PURPOSE: The reliability of the Rockwood classification, the gold standard for acute acromioclavicular (AC) joint separations, has not yet been tested. The purpose of this study was to investigate the reliability of visual and measured AC joint lesion grades according to the Rockwood classification. METHODS: Four investigators (two shoulder specialists and two second-year residents) examined radiographs (bilateral panoramic stress and axial views) in 58 patients and graded the injury according to the Rockwood classification using the following sequence: (1) visual classification of the AC joint lesion, (2) digital measurement of the coracoclavicular distance (CCD) and the horizontal dislocation (HD) with Osirix Dicom Viewer (Pixmeo, Switzerland), (3) classification of the AC joint lesion according to the measurements and (4) repetition of (1) and (2) after repeated anonymization by an independent physician. Visual and measured Rockwood grades as well as the CCD and HD of every patient were documented, and a CC index was calculated (CCD injured/CCD healthy). All records were then used to evaluate intra- and interobserver reliability. RESULTS: The disagreement between visual and measured diagnosis ranged from 6.9 to 27.6 %. Interobserver reliability for visual diagnosis was good (0.72-0.74) and excellent (0.85-0.93) for measured Rockwood grades. Intraobserver reliability was good to excellent (0.67-0.93) for visual diagnosis and excellent for measured diagnosis (0.90-0.97). The correlations between measurements of the axial view varied from 0.68 to 0.98 (good to excellent) for interobserver reliability and from 0.90 to 0.97 (excellent) for intraobserver reliability. CONCLUSION: Bilateral panoramic stress and axial radiographs are reliable examinations for grading AC joint injuries according to Rockwood's classification. Clinicians of all experience levels can precisely classify AC joint lesions according to the Rockwood classification. We recommend to grade acute ACG lesions by performing a digital measurement instead of a sole visual diagnosis because of the higher intra- and interobserver reliability. LEVEL OF EVIDENCE: Case series, Level IV.

Patterns of early resuscitation associated with mortality after penetrating injuries.

BACKGROUND: Penetrating injuries are rare in European populations so their management represents a particular challenge. The aim was to assess early therapeutic aspects that are associated with favourable outcomes in patients with penetrating trauma. METHODS: Patients with penetrating injuries documented from 2009 to 2013 in the TraumaRegister DGU® were analysed. Patients with a primary admission and an Injury Severity Score (ISS) of at least 9 were included. The Revised Injury Severity Classification (RISC) II score was used for mortality prediction, and a standardized mortality ratio (SMR) calculated per hospital. Hospitals with favourable outcome (SMR below 1) were compared with those with poor outcome (SMR 1 or more). RESULTS: A total of 50 centres had favourable outcome (1242 patients; observed mortality rate 15.7 per cent) and 34 centres had poor outcome (918 patients; observed mortality rate 24.4 per cent). Predicted mortality rates according to RISC-II were 20.4 and 20.5 per cent respectively. Mean(s.d.) ISS values were 22(14) versus 21(14) (P = 0.121). Patients in the favourable outcome group had a significantly shorter time before admission to hospital and a lower intubation rate. They received smaller quantities of intravenous fluids on admission to the emergency room, but larger amounts of fresh frozen plasma, and were more likely to receive haemostatic agents. A higher proportion of patients in the favourable outcome group were treated in a level I trauma centre. Independent risk factors for hospital death following penetrating trauma identified by multivariable analysis included gunshot injury mechanism and treatment in non-level I centres. CONCLUSION: Among penetrating traumas, gunshot injuries pose an independent risk of death. Treatment of penetrating trauma in a level I trauma centre was significantly and independently associated with lower hospital mortality.

[Acute acromioclavicular joint injuries. Changes in diagnosis and therapy over the last 10 years]. / Die akute Schultereckgelenkverletzung. Diagnostik, Therapie und Entwicklungen der letzten 10 Jahre.

BACKGROUND: The goal of the present study was to summarize current treatment for acute acromioclavicular (AC) joint dislocations. METHOD: In all, 796 orthopedics and/or trauma departments in Germany were identified in the national hospital directory (www.dka.de). Using the respective hospital web sites, the email addresses of the responsible shoulder/sports surgeon or, if not available, the head of department (successful in 746 cases) were identified. Emails with a link to an online survey with 36 questions and two reminders were sent; 60 were undeliverable. Thus, 686 emails probably reached the addressee. A total of 203 colleagues (30%) participated in the survey. Findings were compared to results of the survey published by Bäthis et al. in 2001. RESULTS: More than 90% treat Rockwood I or II injuries conservatively and Rockwood IV to VI injuries surgically. However, 34% answered having never seen a Rockwood VI injury. Of those replying, 73% prefer surgical treatment for Rockwood III injuries. Favored surgical techniques were the hook plate in 44% and the arthoscopic TightRope® in 27%, while 11% prefer coracoclavicular cerclage, 6% AC joint transfixation, 3% minimally invasive AC joint reconstruction (MINAR), 1% coracoclavicular screw fixation, and 8% a completely different procedure. Concerning acute Rockwood III injuries, orthopedics and/or trauma surgeons still prefer surgical treatment but less often than 10 years ago (84%). CONCLUSIONS: Favored techniques have completely changed since 2001 when the majority of physicians preferred AC joint transfixation or coracoclavicular cerclages, both techniques that are hardly used today. The hook plate appears to have become "standard therapy". The arthroscopic TightRope® is the second most common despite being the newest technique.

In vitro and in vivo studies of the biological activity of novel arylimidamides against Trypanosoma cruzi.

Fifteen novel arylimidamides (AIAs) (6 bis-amidino and 9 mono-amidino analogues) were assayed against Trypanosoma cruzi in vitro and in vivo. All the bis-AIAs were more effective than the mono-AIAs, and two analogues, DB1967 and DB1989, were further evaluated in vivo. Although both of them reduced parasitemia, protection against mortality was not achieved. Our results show that the number of amidino-terminal units affects the efficacy of arylimidamides against T. cruzi.

Serum urea:albumin ratio as a prognostic marker in critical patients with non-chronic kidney disease.

Routine laboratory investigations play an important role in estimating the risk of mortality in intensive care unit (ICU) patients. The significance of urea:albumin ratio (UAR) in predicting the stay and mortality of ICU patients is not known. It is a retrospective study of patients admitted to ICU (n = 412) with non-chronic kidney disease (non-CKD). Receiver-operating characteristics (ROC) analysis for predicting mortality was carried out to find area under curve (AUC) and threshold levels. Analysis of survival probability was carried out by Kaplan-Meier method and Log-rank test. The AUC to predict mortality were 0.695, 0.767 and 0.791 for serum albumin, urea and UAR, respectively. The threshold levels for albumin, urea and UAR were 2.8 g/dL, 53 mg/dL, and 23.44 mg/g, respectively. The highest odds ratio (OR) of 9.75 to predict mortality at threshold level was observed for UAR, while OR were 7.0 and 3.62 for serum urea and albumin, respectively. The serum urea above and albumin below threshold level were associated with increase in ICU stay of >3 days but the highest OR of 4.73 to predict stay of >3 days was observed for UAR. Kaplan-Meier survival analysis shows significant (p < 0.001) difference at the threshold value of UAR. Serum urea and albumin are found to be an independent predictor for the mortality and stay; however an increased UAR value is the best parameter in predicting mortality and stay in ICU patients with non-CKD illness.