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Physical Therapy Jan 2022Over the past 3 decades, the volume of human motor learning research has grown enormously. As such, the understanding of motor learning (ie, sustained change in motor...
Over the past 3 decades, the volume of human motor learning research has grown enormously. As such, the understanding of motor learning (ie, sustained change in motor behavior) has evolved. It has been learned that there are multiple mechanisms through which motor learning occurs, each with distinctive features. These mechanisms include use-dependent, instructive, reinforcement, and sensorimotor adaptation-based motor learning. It is now understood that these different motor learning mechanisms contribute in parallel or in isolation to drive desired changes in movement, and each mechanism is thought to be governed by distinct neural substrates. This expanded understanding of motor learning mechanisms has important implications for physical therapy. It has the potential to facilitate the development of new, more precise treatment approaches that physical therapists can leverage to improve human movement. This Perspective describes scientific advancements related to human motor learning mechanisms and discusses the practical implications of this work for physical therapist practice and education.
Topics: Adaptation, Physiological; Humans; Learning; Motor Skills; Physical Therapy Modalities
PubMed: 34718787
DOI: 10.1093/ptj/pzab250 -
Gut Apr 2022Hepatocellular carcinoma (HCC) is increasingly associated with non-alcoholic steatohepatitis (NASH). HCC immunotherapy offers great promise; however, recent data...
OBJECTIVE
Hepatocellular carcinoma (HCC) is increasingly associated with non-alcoholic steatohepatitis (NASH). HCC immunotherapy offers great promise; however, recent data suggests NASH-HCC may be less sensitive to conventional immune checkpoint inhibition (ICI). We hypothesised that targeting neutrophils using a CXCR2 small molecule inhibitor may sensitise NASH-HCC to ICI therapy.
DESIGN
Neutrophil infiltration was characterised in human HCC and mouse models of HCC. Late-stage intervention with anti-PD1 and/or a CXCR2 inhibitor was performed in murine models of NASH-HCC. The tumour immune microenvironment was characterised by imaging mass cytometry, RNA-seq and flow cytometry.
RESULTS
Neutrophils expressing CXCR2, a receptor crucial to neutrophil recruitment in acute-injury, are highly represented in human NASH-HCC. In models of NASH-HCC lacking response to ICI, the combination of a CXCR2 antagonist with anti-PD1 suppressed tumour burden and extended survival. Combination therapy increased intratumoural XCR1 dendritic cell activation and CD8 T cell numbers which are associated with anti-tumoural immunity, this was confirmed by loss of therapeutic effect on genetic impairment of myeloid cell recruitment, neutralisation of the XCR1-ligand XCL1 or depletion of CD8 T cells. Therapeutic benefit was accompanied by an unexpected increase in tumour-associated neutrophils (TANs) which switched from a protumour to anti-tumour progenitor-like neutrophil phenotype. Reprogrammed TANs were found in direct contact with CD8 T cells in clusters that were enriched for the cytotoxic anti-tumoural protease granzyme B. Neutrophil reprogramming was not observed in the circulation indicative of the combination therapy selectively influencing TANs.
CONCLUSION
CXCR2-inhibition induces reprogramming of the tumour immune microenvironment that promotes ICI in NASH-HCC.
PubMed: 35477863
DOI: 10.1136/gutjnl-2021-326259 -
JAMA Feb 2022Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19.... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.
IMPORTANCE
Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies.
OBJECTIVE
To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure.
DESIGN, SETTING, AND PARTICIPANTS
A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021.
INTERVENTIONS
Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475).
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of tracheal intubation or mortality within 30 days.
RESULTS
The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group.
CONCLUSIONS AND RELEVANCE
Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings.
TRIAL REGISTRATION
isrctn.org Identifier: ISRCTN16912075.
Topics: Adult; COVID-19; Cannula; Continuous Positive Airway Pressure; Female; Hospital Mortality; Humans; Intubation, Intratracheal; Length of Stay; Male; Middle Aged; Noninvasive Ventilation; Oxygen Inhalation Therapy; Respiratory Insufficiency
PubMed: 35072713
DOI: 10.1001/jama.2022.0028 -
Avicenna Journal of Phytomedicine 2020The principle of the use of leeches is associated with traditional medicine of many countries and its application has different philosophies for use in different areas... (Review)
Review
OBJECTIVE
The principle of the use of leeches is associated with traditional medicine of many countries and its application has different philosophies for use in different areas of the body. Leeches, with all the benefits, can have dangers.
MATERIALS AND METHODS
A review of complications of leech therapy was done based on English articles indexed in the databases up to July 1, 2018. A strategic search has done independently by members of the research team and then all of the articles were +categorized by subject.
RESULTS
Related articles were mostly case-reports. Complications were divided into five categories including infection, allergy, prolonged bleeding, migration, and others. Infection is the most-reported complication related to leech therapy and has the most participation in infections.
CONCLUSION
Leech therapy can be a therapeutic complementary method if the possible complications are managed properly.
PubMed: 32523877
DOI: No ID Found -
JAMA Nov 2023Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute...
IMPORTANCE
Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage.
OBJECTIVE
To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol.
DESIGN, SETTING, AND PARTICIPANTS
CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US major trauma centers from August 2017 to November 2021. Eligible patients were injured adults requiring activation of the hospital's major hemorrhage protocol with evidence of active hemorrhage, systolic blood pressure less than 90 mm Hg at any time, and receiving at least 1 U of a blood component transfusion.
INTERVENTION
Patients were randomly assigned (in a 1:1 ratio) to receive standard care, which was the local major hemorrhage protocol (reviewed for guideline adherence), or cryoprecipitate, in which 3 pools of cryoprecipitate (6-g fibrinogen equivalent) were to be administered in addition to standard care within 90 minutes of randomization and 3 hours of injury.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause mortality at 28 days in the intention-to-treat population.
RESULTS
Among 1604 eligible patients, 799 were randomized to the cryoprecipitate group and 805 to the standard care group. Missing primary outcome data occurred in 73 patients (principally due to withdrawal of consent) and 1531 (95%) were included in the primary analysis population. The median (IQR) age of participants was 39 (26-55) years, 1251 (79%) were men, median (IQR) Injury Severity Score was 29 (18-43), 36% had penetrating injury, and 33% had systolic blood pressure less than 90 mm Hg at hospital arrival. All-cause 28-day mortality in the intention-to-treat population was 26.1% in the standard care group vs 25.3% in the cryoprecipitate group (odds ratio, 0.96 [95% CI, 0.75-1.23]; P = .74). There was no difference in safety outcomes or incidence of thrombotic events in the standard care vs cryoprecipitate group (12.9% vs 12.7%).
CONCLUSIONS AND RELEVANCE
Among patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empirical high-dose cryoprecipitate to standard care did not improve all cause 28-day mortality.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04704869; ISRCTN Identifier: ISRCTN14998314.
Topics: Adult; Male; Humans; Middle Aged; Female; Hemorrhage; Fibrinogen; Blood Transfusion; Blood Component Transfusion; Wounds, Penetrating
PubMed: 37824155
DOI: 10.1001/jama.2023.21019 -
The New England Journal of Medicine Jul 2020Uterine fibroids, the most common type of tumor among women of reproductive age, are associated with heavy menstrual bleeding, abdominal discomfort, subfertility, and a... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Uterine fibroids, the most common type of tumor among women of reproductive age, are associated with heavy menstrual bleeding, abdominal discomfort, subfertility, and a reduced quality of life. For women who wish to preserve their uterus and who have not had a response to medical treatment, myomectomy and uterine-artery embolization are therapeutic options.
METHODS
We conducted a multicenter, randomized, open-label trial to evaluate myomectomy, as compared with uterine-artery embolization, in women who had symptomatic uterine fibroids and did not want to undergo hysterectomy. Procedural options included open abdominal, laparoscopic, or hysteroscopic myomectomy. The primary outcome was fibroid-related quality of life, as assessed by the score on the health-related quality-of-life domain of the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire (scores range from 0 to 100, with higher scores indicating a better quality of life) at 2 years; adjustment was made for the baseline score.
RESULTS
A total of 254 women, recruited at 29 hospitals in the United Kingdom, were randomly assigned: 127 to the myomectomy group (of whom 105 underwent myomectomy) and 127 to the uterine-artery embolization group (of whom 98 underwent embolization). Data on the primary outcome were available for 206 women (81%). In the intention-to-treat analysis, the mean (±SD) score on the health-related quality-of-life domain of the UFS-QOL questionnaire at 2 years was 84.6±21.5 in the myomectomy group and 80.0±22.0 in the uterine-artery embolization group (mean adjusted difference with complete case analysis, 8.0 points; 95% confidence interval [CI], 1.8 to 14.1; P = 0.01; mean adjusted difference with missing responses imputed, 6.5 points; 95% CI, 1.1 to 11.9). Perioperative and postoperative complications from all initial procedures, irrespective of adherence to the assigned procedure, occurred in 29% of the women in the myomectomy group and in 24% of the women in the uterine-artery embolization group.
CONCLUSIONS
Among women with symptomatic uterine fibroids, those who underwent myomectomy had a better fibroid-related quality of life at 2 years than those who underwent uterine-artery embolization. (Funded by the National Institute for Health Research Health Technology Assessment program; FEMME Current Controlled Trials number, ISRCTN70772394.).
Topics: Adult; Female; Humans; Hysteroscopy; Intention to Treat Analysis; Intraoperative Complications; Laparoscopy; Leiomyoma; Length of Stay; Menorrhagia; Middle Aged; Ovarian Reserve; Postoperative Complications; Quality of Life; Reoperation; Uterine Artery Embolization; Uterine Myomectomy; Uterine Neoplasms; Uterus
PubMed: 32726530
DOI: 10.1056/NEJMoa1914735 -
The Lancet. Haematology Apr 2022Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red... (Randomized Controlled Trial)
Randomized Controlled Trial
Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial.
BACKGROUND
Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock.
METHODS
Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938.
FINDINGS
From Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths.
INTERPRETATION
The trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders.
FUNDING
National Institute for Health Research Efficacy and Mechanism Evaluation.
Topics: Adolescent; Adult; Blood Transfusion; COVID-19; Emergency Medical Services; Humans; Male; Middle Aged; Pandemics; Shock, Hemorrhagic; Treatment Outcome
PubMed: 35271808
DOI: 10.1016/S2352-3026(22)00040-0 -
Journal of Ayurveda and Integrative... 2020Medicinal leech therapy or Hirudino therapy have roots back in ancient civilization. It was a prevalent form of therapy in various ailments. The novel Ayurveda text... (Review)
Review
Medicinal leech therapy or Hirudino therapy have roots back in ancient civilization. It was a prevalent form of therapy in various ailments. The novel Ayurveda text Sushruta Samhita devoted a complete chapter on hirudino therapy. In the early 20th century this therapy had a major setback due to origin and evolution of antibiotics. There was a discontinuity in the flow of knowledge about this therapy. Then, resumed and revived after few recent decades, due to its contribution in reconstructive surgeries. During this period, the research work on various aspects have been conducted. The present paper summarizes the various aspects of medicinal leech therapy both from Ayurveda text and the present knowledge and to enable the fraternity to use the both source for benefits of humankind.
PubMed: 30709686
DOI: 10.1016/j.jaim.2018.09.003 -
The Lancet. Oncology Nov 2021Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system... (Clinical Trial)
Clinical Trial
BACKGROUND
Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction.
METHODS
This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20-60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926.
FINDINGS
Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16-30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77-0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50-0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80-0·88; p<0·001), and full lockdowns (0·57, 0·54-0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays.
INTERPRETATION
Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services.
FUNDING
National Institute for Health Research Global Health Research Unit, Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, Medtronic, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.
Topics: Adult; Aged; Aged, 80 and over; COVID-19; Communicable Disease Control; Female; Humans; Male; Middle Aged; Neoplasms; Outcome Assessment, Health Care; Proportional Hazards Models; Prospective Studies; SARS-CoV-2; Time-to-Treatment; Withholding Treatment
PubMed: 34624250
DOI: 10.1016/S1470-2045(21)00493-9 -
European Heart Journal Mar 2021Women undergo important changes in sex hormones throughout their lifetime that can impact cardiovascular disease risk. Whereas the traditional cardiovascular risk...
Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists.
Women undergo important changes in sex hormones throughout their lifetime that can impact cardiovascular disease risk. Whereas the traditional cardiovascular risk factors dominate in older age, there are several female-specific risk factors and inflammatory risk variables that influence a woman's risk at younger and middle age. Hypertensive pregnancy disorders and gestational diabetes are associated with a higher risk in younger women. Menopause transition has an additional adverse effect to ageing that may demand specific attention to ensure optimal cardiovascular risk profile and quality of life. In this position paper, we provide an update of gynaecological and obstetric conditions that interact with cardiovascular risk in women. Practice points for clinical use are given according to the latest standards from various related disciplines (Figure 1).
Topics: Aged; Cardiologists; Cardiovascular Diseases; Consensus; Endocrinologists; Female; Humans; Menopause; Middle Aged; Pregnancy; Quality of Life; Risk Factors
PubMed: 33495787
DOI: 10.1093/eurheartj/ehaa1044