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Andrology Jan 2021Recent epidemiological data indicate that there may be a gender predisposition to COVID-19, with men predisposed to being most severely affected, and older men...
BACKGROUND
Recent epidemiological data indicate that there may be a gender predisposition to COVID-19, with men predisposed to being most severely affected, and older men accounting for most deaths.
OBJECTIVES
Provide a review of the research literature, propose hypotheses, and therapies based on the potential link between testosterone (T) and COVID-19 induced mortality in elderly men.
MATERIALS AND METHODS
A search of publications in academic electronic databases, and government and public health organization web sites on T, aging, inflammation, severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) infection, and COVID-19 disease state and outcomes was performed.
RESULTS
The link between T, the immune system, and male aging is well-established, as is the progressive decline in T levels with aging. In women, T levels drop before menopause and variably increase with advanced age. Elevated IL-6 is a characteristic biomarker of patients infected with COVID-19 and has been linked to the development of the acute respiratory distress syndrome (ARDS). Thus far, half of the admitted COVID-19 patients developed ARDS, half of these patients died, and elderly male patients have been more likely to develop ARDS and die. Low T is associated with ARDS. These data suggest that low T levels may exacerbate the severity of COVID-19 infection in elderly men. It may also stand to reason that normal T levels may offer some protection against COVID-19. SARS-CoV-2 binds to the angiotensin-converting enzyme 2, present in high levels in the testis.
CONCLUSION
At present, it is not known whether low T levels in aging hypogonadal males create a permissive environment for severe responses to COVID-19 infection or if the virus inhibits androgen formation. Given the preponderance of COVID-19 related mortality in elderly males, additional testing for gonadal function and treatment with T may be merited.
Topics: Age Factors; Aged; Aged, 80 and over; COVID-19; Female; Health Status Disparities; Host-Pathogen Interactions; Humans; Male; Middle Aged; Prognosis; Risk Assessment; Risk Factors; SARS-CoV-2; Sex Factors; Testosterone
PubMed: 32681716
DOI: 10.1111/andr.12868 -
European Journal of Trauma and... Apr 2018Permissive hypotensive resuscitation (PHR) is an advancing concept aiming towards deliberative balanced resuscitation whilst treating severely injured patients, and its... (Review)
Review
BACKGROUND
Permissive hypotensive resuscitation (PHR) is an advancing concept aiming towards deliberative balanced resuscitation whilst treating severely injured patients, and its effectiveness on the survival rate remains unexplored. This detailed systematic review aims to critically evaluate the available literature that investigates the effects of PHR on survival rate.
METHODS
A systematic review design searched for comparative and non-comparative studies using EMBASE, MEDLINE, PubMed, Web-of-Science and CENTRAL. Full-text articles on adult trauma patients with low blood pressure were considered for inclusion. The risk of bias and a critical appraisal of the identified articles were performed to assess the quality of the selected studies. Included studies were sorted into comparative and non-comparative studies to ease the process of analysis. Mortality rates of PHR were calculated for both groups of studies.
RESULTS
From the 869 articles that were initially identified, ten studies were selected for review, including randomised control trials (RCTs) and cohort studies. By applying the risk of bias assessment and critique tools, the methodologies of the selected articles ranged from moderate to high quality. The mortality rates among patients resuscitated with low volume and large volume in the selected RCTs were 21.5% (123/570) and 28.6% (168/587) respectively, whilst the total mortality rate of the patients enrolled in three non-comparative studies was 9.97% (279/2797).
CONCLUSIONS
The death rate amongst post-trauma patients managed with conservative resuscitation was lower than standard aggressive resuscitation, which indicates that PHR can create better survival rate among traumatised patients. Therefore, PHR is a feasible and safely practiced fluid resuscitative strategy to manage haemorrhagic shock in pre-hospital and in-hospital settings. Further trials on PHR are required to assess its effectiveness on the survival rate.
LEVEL OF EVIDENCE
Systematic review, level III.
Topics: Adult; Humans; Multiple Trauma; Resuscitation; Shock, Hemorrhagic; Survival Analysis
PubMed: 29079917
DOI: 10.1007/s00068-017-0862-y -
Nutrition in Clinical Practice :... Jun 2018The aim of this study was to systematically review the effect of permissive underfeeding/trophic feeding on the clinical outcomes of critically ill patients. A...
Permissive or Trophic Enteral Nutrition and Full Enteral Nutrition Had Similar Effects on Clinical Outcomes in Intensive Care: A Systematic Review of Randomized Clinical Trials.
The aim of this study was to systematically review the effect of permissive underfeeding/trophic feeding on the clinical outcomes of critically ill patients. A systematic review of randomized clinical trials to evaluate the mortality, length of stay, and mechanical ventilation duration in patients randomized to either hypocaloric or full-energy enteral nutrition was performed. Data sources included PubMed and Scopus and the reference lists of the articles retrieved. Two independent reviewers participated in all phases of this systematic review as proposed by the Cochrane Handbook, and the review was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 7 randomized clinical trials that included a total of 1,717 patients were reviewed. Intensive care unit length of stay and mechanical ventilation duration were not statistically different between the intervention and control groups in all randomized clinical trials, and mortality rate was also not different between the groups. In conclusion, hypocaloric enteral nutrition had no significantly different effects on morbidity and mortality in critically ill patients when compared with full-energy nutrition. It is still necessary to determine the safety of this intervention in this group of patients, the optimal amount of energy provided, and the duration of this therapy.
Topics: Critical Care; Critical Illness; Enteral Nutrition; Humans; Length of Stay; Nutritional Status; Randomized Controlled Trials as Topic; Respiration, Artificial; Treatment Outcome
PubMed: 29377333
DOI: 10.1002/ncp.10001 -
Plastic and Reconstructive Surgery.... Mar 2022Functional recovery after peripheral nerve injury is often suboptimal despite the intrinsic permissive growth environment of the peripheral nervous system. The objective...
UNLABELLED
Functional recovery after peripheral nerve injury is often suboptimal despite the intrinsic permissive growth environment of the peripheral nervous system. The objective of this systematic review is to explore the use of electrical stimulation (ES) for peripheral nerve regeneration.
METHODS
A systematic literature search was conducted from inception to March 2, 2021 to retrieve articles on ES for peripheral nerve regeneration using the PubMed, Ovid MEDLINE, and Embase databases. Primary outcome measures included objective measures of motor and sensory nerve function.
RESULTS
Four randomized control trials, two case reports, and three case series that addressed the aims were identified. The stimulation parameters varied greatly between studies, without an apparent commonality for a given electrical conduit. Outcomes measured included motor (n = 8) and sensory (n = 7) modalities (cold detection, static two-point discrimination, tactile discrimination, and pressure detection), nerve-specific muscle function and bulk, and electromyography (EMG) motor and sensory terminal latency. Different parameters for measurement were utilized and improvement was observed across the studies compared with controls (n = 4) or pre-intervention measurements (n = 5). One randomized control trial reported no benefit of ES and attributed their findings to their stimulation protocol. Complications were documented in three patients only and included wire remnant removal, skin pigmentation, and bone formation.
CONCLUSIONS
ES in peripheral nerve regeneration is beneficial in improving and accelerating recovery. A meta-analysis was not performed due to the heterogeneity, but all studies showed positive findings and minor to no complications. These results provide a primer for further development of delivery methods.
PubMed: 35317464
DOI: 10.1097/GOX.0000000000004115 -
Progres En Urologie : Journal de... Dec 2020Clinical trials of cell therapy for erectile dysfunction (ED) and Peyronie's disease (PD) were recently conducted after preclinical studies.
INTRODUCTION
Clinical trials of cell therapy for erectile dysfunction (ED) and Peyronie's disease (PD) were recently conducted after preclinical studies.
AIMS
The aims of this study are to give an update on biotherapy for ED and PD and to describe the regulatory framework for these therapies.
MATERIALS AND METHODS
A literature review was performed through PubMed and Clinical.trials.gov addressing cell therapy for ED and PD and using following keywords "erectile dysfunction", "Peyronie's disease", "stem cell", and "platelet-rich plasma".
RESULTS
Preclinical studies in rodent models have shown the potential benefit of cell therapy for ED after radical prostatectomy or caused by metabolic diseases, and PD. The tissues used to obtain the therapeutic product were bone marrow, adipose tissue and blood (PRP, platelet-rich plasma). Mechanism of action was shown to be temporary and mainly paracrine. Four clinical trials were published concerning ED after radical prostatectomy and in diabetic patients and one for PD. Eleven clinical trials including three randomized trials are currently going on. Preclinical and preliminary clinical results suggested the possibility to improve spontaneous erectile function and response to pharmaceutical treatment in initially non-responder patients. This effect is mediated by an improvement of penile vascularization. A reduction of penile curvature without side effect was noted after injections into the plaque of PD patients. Most of these therapeutic strategies using autologous cells were considered as "Advanced Therapy Medicinal Products" with strict regulatory frameworks imposing heavy constraints, in particular in case of "substantial" modification of the cells. The regulatory framework remains unclear and more permissive for PRP and cell therapy processes with extemporaneous preparation/injection and no "substantial" modifications.
CONCLUSIONS
First results on cell therapy for ED and PD are promising. The regulatory framework can significantly change according to cell preparations and origins leading to various constraints. This regulatory framework is crucial to consider for the choice of the procedure.
Topics: Biological Therapy; Clinical Trials as Topic; Erectile Dysfunction; Humans; Male; Penile Induration; Stem Cell Transplantation
PubMed: 32826194
DOI: 10.1016/j.purol.2020.05.002 -
Journal of Intensive Care Jan 2024Our previous study in 2011 concluded that permissive underfeeding may improve outcomes in patients receiving parenteral nutrition therapy. This conclusion was tentative,...
BACKGROUND
Our previous study in 2011 concluded that permissive underfeeding may improve outcomes in patients receiving parenteral nutrition therapy. This conclusion was tentative, given the small sample size. We conducted the present systematic review and trial sequential meta-analysis to update the status of permissive underfeeding in patients who were admitted to the intensive care unit (ICU).
METHODS
Seven databases were searched: PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database, and Cochrane Library. Randomized controlled trials (RCTs) were included. The Revised Cochrane risk-of-bias tool (ROB 2) was used to assess the risk of bias in the enrolled trials. RevMan software was used for data synthesis. Trial sequential analyses (TSA) of overall and ICU mortalities were performed.
RESULTS
Twenty-three RCTs involving 11,444 critically ill patients were included. There were no significant differences in overall mortality, hospital mortality, length of hospital stays, and incidence of overall infection. Compared with the control group, permissive underfeeding significantly reduced ICU mortality (risk ratio [RR] = 0.90; 95% confidence interval [CI], [0.81, 0.99]; P = 0.02; I = 0%), and the incidence of gastrointestinal adverse events decreased (RR = 0.79; 95% CI, [0.69, 0.90]; P = 0.0003; I = 56%). Furthermore, mechanical ventilation duration was reduced (mean difference (MD) = - 1.85 days; 95% CI, [- 3.44, - 0.27]; P = 0.02; I = 0%).
CONCLUSIONS
Permissive underfeeding may reduce ICU mortality in critically ill patients and help to shorten mechanical ventilation duration, but the overall mortality is not improved. Owing to the sample size and patient heterogeneity, the conclusions still need to be verified by well-designed, large-scale RCTs. Trial Registration The protocol for our meta-analysis and systematic review was registered and recorded in PROSPERO (registration no. CRD42023451308). Registered 14 August 2023.
PubMed: 38254228
DOI: 10.1186/s40560-024-00717-3 -
The Cochrane Database of Systematic... 2001Experimental animal data and uncontrolled, observational studies in human infants have suggested that hyperventilation and hypocapnia may be associated with increased... (Review)
Review
BACKGROUND
Experimental animal data and uncontrolled, observational studies in human infants have suggested that hyperventilation and hypocapnia may be associated with increased pulmonary and neurodevelopmental morbidity. Protective ventilatory strategies allowing higher levels of arterial CO2 (permissive hypercapnia) are now widely used in adult critical care. The aggressive pursuit of normocapnia in ventilated newborn infants may contribute to the already present burden of lung disease. However, the safe or ideal range for PCO2 in this vulnerable population has not been established.
OBJECTIVES
To assess whether, in mechanically ventilated neonates, a strategy of permissive hypercapnia improves short and long term outcomes (esp. mortality, duration of respiratory support, incidence of chronic lung disease and neurodevelopmental outcome).
SEARCH STRATEGY
Standard strategies of the Cochrane Neonatal Review Group were used. Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, CINAHL, and Current Contents. Searches were also made of previous reviews including cross-referencing, abstracts, and conference and symposia proceedings published in Pediatric Research.
SELECTION CRITERIA
All randomised controlled trials in which a strategy of permissive hypercapnia was compared with conventional strategies aimed at achieving normocapnia (or lower levels of hypercapnia) in newborn infants who are mechanically ventilated were eligible.
DATA COLLECTION AND ANALYSIS
Standard methods of the Cochrane Neonatal Review Group were used. Trials identified by the search strategy were independently reviewed by each author and assessed for eligibility and trial quality. Data were extracted separately. Differences were compared and resolved. Additional information was requested from trial authors. Only published data were available for review. Results are expressed as relative risk and risk difference for dichotomous outcomes, and weighted mean difference for continuous variables.
MAIN RESULTS
Two trials involving 269 newborn infants were included. Meta-analysis of combined data was possible for three outcomes. There was no evidence that permissive hypercapnia reduced the incidence of death or chronic lung disease at 36 weeks (RR 0.94, 95% CI 0.78, 1.15), intraventricular haemorrhage grade 3 or 4 (RR 0.84, 95% CI 0.54, 1.31) or periventricular leukomalacia (RR 1.02, 95% CI 0.49, 2.12). There were no differences in any other reported outcomes when the strategy of permissive hypercapnia/minimal ventilation was compared to routine ventilation in newborn infants. Long term neurodevelopmental outcomes were not reported. One trial reported that permissive hypercapnia reduced the incidence of chronic lung disease in the 501 to 750 gram subgroup.
REVIEWER'S CONCLUSIONS
This review does not demonstrate any significant overall benefit of a permissive hypercapnia/minimal ventilation strategy compared to a routine ventilation strategy. At present, therefore, these ventilation strategies cannot be recommended to reduce mortality, or pulmonary and neurodevelopmental morbidity. Ventilatory strategies which target high levels of PCO2 (> 55 mmHg) should only be undertaken in the context of well-designed controlled clinical trials. These trials should aim to establish the safe, or ideal, range for CO2 in ventilated newborns, and examine the role of protective ventilatory techniques in achieving this target.
Topics: Bronchopulmonary Dysplasia; Carbon Dioxide; Cerebral Hemorrhage; Chronic Disease; Humans; Infant Mortality; Infant, Newborn; Leukomalacia, Periventricular; Lung Diseases; Randomized Controlled Trials as Topic; Respiration; Respiration, Artificial; Retinopathy of Prematurity
PubMed: 11406029
DOI: 10.1002/14651858.CD002061 -
Critical Care Medicine Nov 2004In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for mechanical ventilation in... (Review)
Review
OBJECTIVE
In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for mechanical ventilation in sepsis-induced acute lung injury/acute respiratory distress syndrome (ARDS) that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis.
DESIGN
The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee.
METHODS
The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591.
CONCLUSION
A minimum amount of positive end-expiratory pressure should be set to prevent lung collapse at end expiration in ARDS. Setting the level of positive end-expiratory pressure may be guided by Fio2 requirement or measurement of thoracopulmonary compliance. Role of noninvasive positive-pressure ventilation in acute lung injury/ARDS is undefined. Small tidal volume ventilation and limitation of end-inspiratory plateau pressure is important in the management of ARDS and may be facilitated by permissive hypercapnia. Prone positioning should be considered in the severest of ARDS patients. The ideal fluid management strategy in ARDS is unknown. Weaning protocols should be in place that include spontaneous breathing trials and criteria for initiating such trials. The role of high-frequency oscillatory ventilation and airway pressure release ventilation in ARDS is uncertain.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Carbon Dioxide; Consensus Development Conferences as Topic; Continuous Positive Airway Pressure; Evidence-Based Medicine; Fluid Therapy; Humans; Nitric Oxide; Partial Pressure; Positive-Pressure Respiration; Practice Guidelines as Topic; Prone Position; Respiration, Artificial; Respiratory Distress Syndrome; Sepsis; Tidal Volume
PubMed: 15542963
DOI: 10.1097/01.ccm.0000145947.19077.25 -
Frontiers in Physiology 2022Striated muscle contraction is inhibited by the actin associated proteins tropomyosin, troponin T, troponin I and troponin C. Binding of Ca to troponin C relieves this...
Striated muscle contraction is inhibited by the actin associated proteins tropomyosin, troponin T, troponin I and troponin C. Binding of Ca to troponin C relieves this inhibition by changing contacts among the regulatory components and ultimately repositioning tropomyosin on the actin filament creating a state that is permissive for contraction. Several lines of evidence suggest that there are three possible positions of tropomyosin on actin commonly called Blocked, Closed/Calcium and Open or Myosin states. These states are thought to correlate with different functional states of the contractile system: inactive-Ca-free, inactive-Ca-bound and active. The inactive-Ca-free state is highly occupied at low free Ca levels. However, saturating Ca produces a mixture of inactive and active states making study of the individual states difficult. Disease causing mutations of troponin, as well as phosphomimetic mutations change the stabilities of the states of the regulatory complex thus providing tools for studying individual states. Mutants of troponin are available to stabilize each of three structural states. Particular attention is given to the hypertrophic cardiomyopathy causing mutation, Δ14 of TnT, that is missing the last 14 C-terminal residues of cardiac troponin T. Removal of the basic residues in this region eliminates the inactive-Ca-free state. The major state occupied with Δ14 TnT at inactivating Ca levels resembles the inactive-Ca-bound state in function and in displacement of TnI from actin-tropomyosin. Addition of Ca, with Δ14TnT, shifts the equilibrium between the inactive-Ca-bound and the active state to favor that latter state. These mutants suggest a unique role for the C-terminal region of Troponin T as a brake to limit Ca activation.
PubMed: 35694406
DOI: 10.3389/fphys.2022.902079 -
International Journal of Infectious... Jun 2012Although the application of cardiac implantable electronic devices (CIED) has greatly increased over the past few decades, CIED endocarditis is becoming a challenging... (Review)
Review
OBJECTIVES
Although the application of cardiac implantable electronic devices (CIED) has greatly increased over the past few decades, CIED endocarditis is becoming a challenging scenario in clinical practice. Recently, Staphylococcus lugdunensis has emerged as a pathogen in CIED endocarditis. However, a detailed phenotypic characterization has not been addressed.
METHODS
We conducted a systematic literature review covering the period between 1989 and 2011 using the PubMed, Medline, Cochrane, and Embase databases. All cases included had a CIED in use and met the modified Duke criteria for infective endocarditis, and all had isolates of S. lugdunensis. The clinical features, predisposing conditions, echocardiographic findings, and therapeutic strategies/outcomes were evaluated. Polymorphonuclear neutrophil functions were examined to test whether the defect of innate immunity may play a permissive role in host susceptibility to tissue destruction in S. lugdunensis endocarditis.
RESULTS
Eleven patients with CIED endocarditis caused by S. lugdunensis were identified. Their mean age was 61.7±11.2 years, and there was a male preponderance (72.7%). Six patients (54.5%) had undergone re-manipulation of the pacing system within a few months to years before the occurrence of clinical symptoms. The median time of symptoms before the diagnosis of CIED endocarditis was 60 days. On echocardiography, vegetations in the CIED were detected in nine cases (81.8%). Nine patients (81.8%) underwent surgical removal of the entire device, and one patient received medical treatment alone. The overall mortality rate was 18.2%. One patient had a septic perforation of the ventricular septum, with a high serum level of N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP) in the absence of pump failure. The assessment of polymorphonuclear neutrophil (PMN) functions revealed normal PMN responses to the various stimuli and normal oxidative burst responses.
CONCLUSIONS
Identification and differentiation of staphylococcal species in a timely manner would allow us to intervene more aggressively at an earlier stage to prevent unfavorable outcomes. Clinicians should never consider the isolation of S. lugdunensis as contamination. In selected individuals, therapeutic abstention may be preferable to exposing patients to a high risk of S. lugdunensis CIED endocarditis due to re-manipulation of the pacing system. The prognostic value of NT-pro-BNP warrants further investigations.
Topics: Aged; Device Removal; Echocardiography; Endocarditis, Bacterial; Female; Humans; Natriuretic Peptide, Brain; Neutrophils; Pacemaker, Artificial; Peptide Fragments; Prosthesis-Related Infections; Reoperation; Risk Factors; Staphylococcal Infections; Staphylococcus lugdunensis; Time Factors; Ultrasonography, Doppler, Color
PubMed: 22497965
DOI: 10.1016/j.ijid.2012.02.010