COVID-19 infection: the perspectives on immune responses.
Cell death and differentiation. 2020;27(5):1451-1454
Plain language summary
The SARS-CoV-2 infection triggers an immune response which varies greatly from one person to another. It can be roughly divided into three stages: stage I, an asymptomatic incubation period with or without detectable virus; stage II, non-severe symptomatic period with the presence of virus; stage III, severe respiratory symptomatic stage with high viral load. Currently around 15% of people infected end up in severe stage III. There appears to be a two-phase immune response; an early protective phase and a second inﬂammation-driven damaging phase. In phase one the adaptive immune system responds to the virus. Being in good general health is important in this phase to limiting the progression of the disease to a more severe stage. In phase two the innate immune system response to tissue damage caused by the virus could lead to widespread inflammation of the lungs and acute respiratory distress syndrome or respiratory failure. Therapeutically this raises the question of whether the immune response should be boosted in phase one and suppressed in phase two. There also appears to be an element of viral relapse in some patients discharged from hospital indicating that a virus-eliminating immune response may be difficult to achieve naturally. These same patients may also not respond to vaccines. Overall, it is still unclear why some people develop severe disease, whilst others do not. Overall immunity alone does not explain the differences in disease presentation.
Modulatory effects of different exercise modalities on the functional connectivity of the periaqueductal grey and ventral tegmental area in patients with knee osteoarthritis: a randomised multimodal magnetic resonance imaging study.
British journal of anaesthesia. 2019;(4):506-518
BACKGROUND Knee osteoarthritis is a prevalent disorder with unsatisfactory treatment options. Both physical and mindful exercises may be able to relieve its pain symptoms. We compared the modulatory effects of different exercise modalities on the periaqueductal grey (PAG) and ventral tegmental area (VTA), which play important roles in descending opioidergic pathways and reward/motivation systems in patients with knee osteoarthritis. METHODS We recruited and randomised 140 patients into Tai Chi, Baduanjin, stationary cycling, and health education control groups for 12 weeks. Knee injury and Osteoarthritis Outcome Score (KOOS), functional and structural MRI, and blood biomarkers were measured at the beginning and end of the experiment. We used the PAG and VTA as seeds in resting-state functional connectivity (rsFC) analysis. RESULTS Compared with the control group: (i) all exercises significantly increased KOOS pain sub-scores (pain reduction) and serum programmed death 1 (PD-1) concentrations; (ii) all exercises decreased right PAG rsFC with the medial orbital prefrontal cortex, and the decreased rsFC was associated with improvements in knee pain; and (iii) grey matter volume in the medial orbital prefrontal cortex was significantly increased in all exercise groups. There was also significantly decreased rsFC between the left VTA and the medial orbital prefrontal cortex in the Tai Chi and Baduanjin groups. CONCLUSIONS Exercise can simultaneously modulate the rsFC of the descending opioidergic pathway and reward/motivation system and blood inflammation markers. Elucidating the shared and unique mechanisms of different exercise modalities may facilitate the development of exercise-based interventions for chronic pain. CLINICAL TRIAL REGISTRATION ChiCTR-IOR-16009308.
Different exercise modalities relieve pain syndrome in patients with knee osteoarthritis and modulate the dorsolateral prefrontal cortex: A multiple mode MRI study.
Brain, behavior, and immunity. 2019;:253-263
OBJECTIVES Knee osteoarthritis (KOA) is a common degenerative joint disease with no satisfactory intervention. Recently, both physical and mindfulness exercises have received considerable attention for their implications in KOA pain management, and the dorsolateral prefrontal cortex (DLPFC) has displayed a critical role in pain modulation. This study aimed to comparatively investigate the modulation effects of different exercises using multidisciplinary measurements. METHODS 140 KOA patients were randomized into Tai Chi, Baduanjin, stationary cycling, or health education control groups for 12 weeks. Knee Injury and Osteoarthritis Outcome Score (KOOS), resting state functional magnetic resonance imaging (fMRI), structural MRI, and serum biomarkers were measured at baseline and at the end of the study. RESULTS We found: 1) increased KOOS pain subscores (pain reduction) and serum programmed cell death protein 1 (PD-1) levels in the three exercise groups compared to the control group; 2) decreased resting state functional connectivity (rsFC) of the DLPFC-supplementary motor area (SMA) and increased rsFC between the DLPFC and anterior cingulate cortex in all exercise groups compared to the control group; 3) significant associations between DLPFC-SMA rsFC with KOOS pain subscores and serum PD-1 levels at baseline; 4) significantly increased grey matter volume in the SMA in the Tai Chi and stationary cycling groups, and a trend toward significant increase in the Baduanjin group compared to the control group; 5) significant DLPFC rsFC differences among different exercise groups; and 6) that baseline DLPFC-SMA rsFC can predict the effect of mind-body exercise on pain improvement in KOA. CONCLUSION Our results suggest that different exercises can modulate both common and unique DLPFC (cognitive control) pathways, and altered DLPFC-SMA rsFC is associated with serum biomarker levels. Our findings also highlight the potentials of neuroimaging biomarkers in predicting the therapeutic effect of mind-body exercises on KOA pain.
Three Nurse-administered Protocols Reduce Nutritional Decline and Frailty in Older Gastrointestinal Surgery Patients: A Cluster Randomized Trial.
Journal of the American Medical Directors Association. 2019;(5):524-529.e3
OBJECTIVE To evaluate the effects of the modified Hospital Elder Life Program (mHELP) comprising 3 nurse-administered protocols in older patients undergoing gastrointestinal (GI) surgery. DESIGN Cluster randomized trial. SETTING Two 36-bed GI wards at a university-affiliated medical center in Taiwan. PARTICIPANTS Older patients (≥65 years, N = 377) were recruited if they were scheduled for elective GI surgery with an expected length of hospital stay >6 days. After transferring to the GI ward after surgery, participants were randomly assigned to the mHELP or control group (1:1) by room rather than individually because most patient units are double- or triple-occupancy rooms. INTERVENTION The mHELP protocols (early mobilization, oral and nutritional assistance, and orienting communication) were administered daily with usual care by a trained nurse until hospital discharge. The control group received usual care only. MEASURES Outcomes were in-hospital nutritional decline, measured by body weight and Mini-Nutritional Assessment (MNA) scores, and Fried's frailty phenotype. Return of GI motility was examined as a potential mechanism contributing to observed outcomes. RESULTS Participants (mean age = 74.5 years; 56.8% male) primarily underwent colorectal (56.5%), gastric (21.2%), and pancreatobiliary (13.8%) surgery. Participants who received the mHELP [for a median of 7 days (interquartile range = 6-10 days)] had significantly lower in-hospital weight loss and decline in MNA scores (weight -2.1 vs -4.0 lb, P = .002; score -3.2 vs -4.0, P = .03) than the control group. The mHELP group also had significantly lower rates of incident frailty during hospitalization (12.0% vs 21.7%, P = .022), and persistent frailty (50.0% vs 92.9%, P = .03). Participants in the mHELP group had trends toward an accelerated return of GI motility. CONCLUSION AND IMPLICATIONS The mHELP effectively reduced nutritional decline, prevented new frailty, and promoted recovery of frailty present before admission. These nurse-administered protocols might be useful in other settings, including conditions managed at home or in nursing facilities.
Mixed Spices at Culinary Doses Have Prebiotic Effects in Healthy Adults: A Pilot Study.
Plain language summary
An increasing body of evidence suggests that the gut microbiota has a profound impact on human health. While the microbiome of a healthy individual is relatively stable, gut microbial dynamics can be influenced by host lifestyle and dietary choices. The aim of this study was to investigate the effects of mixed spices (cinnamon, oregano, ginger, black pepper, and cayenne pepper) at culinary doses consumed over 2 weeks in a standardized 5g capsule on the production of gut microbiota and short-chain fatty acids The study is a randomised, placebo-controlled, double-blind pilot study carried out with a total of 31 healthy women and men aged between 18 and 65. The subjects were randomly allocated to one of the two intervention groups. Results indicate that daily intake of 5g of mixed spices for 2 weeks in healthy subjects resulted in a significant reduction in the relative abundance of the phylum Firmicutes (bacteria), and a trend of increasing in phylum Bacteroidetes (bacteria) as compared with a matched control group. Authors conclude that a mixture of spices at culinary doses affects the composition of gut microbiota.
undefined: Spices were used as food preservatives prior to the advent of refrigeration, suggesting the possibility of effects on microbiota. Previous studies have shown prebiotic activities in animals and in vitro, but there has not been a demonstration of prebiotic or postbiotic effects at culinary doses in humans. In this randomized placebo-controlled study, we determined in twenty-nine healthy adults the effects on the gut microbiota of the consumption daily of capsules containing 5 g of mixed spices at culinary doses by comparison to a matched control group consuming a maltodextrin placebo capsule. The 16S ribosomal RNA sequencing data were used for microbial characterization. Spice consumption resulted in a significant reduction in Firmicutes abundance ( < 0.033) and a trend of enrichment in Bacteroidetes ( < 0.097) compared to placebo group. Twenty-six operational taxonomic units (OTUs) were different between the spice and placebo groups after intervention. Furthermore, there was a significant negative correlation between fecal short-chain fatty acid propionate concentration and Firmicutes abundance in spice intervention group ( < 0.04). The production of individual fecal short-chain fatty acid was not significantly changed by spice consumption in this study. Mixed spices consumption significantly modified gut microbiota, suggesting a prebiotic effect of spice consumption at culinary doses.
Quadriceps combined with hip abductor strengthening versus quadriceps strengthening in treating knee osteoarthritis: a study protocol for a randomized controlled trial.
BMC musculoskeletal disorders. 2018;(1):147
BACKGROUND Lower limb strengthening, especially the quadriceps training, is of much necessity for patients with knee osteoarthritis (KOA). Previous studies suggest that strengthening of the hip muscles, especially the hip abductor, can potentially relieve the KOA-associated symptoms. Nevertheless, the effects of quadriceps combined with hip abductor strengthening remain unclear. Therefore, the current randomized controlled trial is designed aiming to observe whether quadriceps in combination with hip abductor strengthening can better improve the function and reduce pain in KOA patients than quadriceps training alone. METHODS A total of 80 subjects with symptomatic KOA will be recruited from the communities and hospital outpatient, and will be randomly assigned to the experiment group (Quadriceps-plus-hip-abductor-strengthening) or the control group (Quadriceps-strengthening). Specifically, participants in the experiment group will complete 4 exercises to train the quadriceps and hip abductor twice a day for 6 weeks at home, while those in the control group will only perform 2 exercises to strengthen the quadriceps. Besides, all patients will also receive usual care management, including health education and physical agent therapy when necessary. Knee pain will be measured using the Visual Analogue Scale (VAS) at baseline, in every week during the course of treatment, as well as 8 and 12 weeks after randomization. Furthermore, knee function will be measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale, and the quality of life will be measured using the MOS Item Short-form Health Survey (SF-36). In this study, several simple tests will be applied to assess the objective function. All the assessments except for VAS will be carried out at baseline, and in the 6th, 8th and 12th weeks respectively. DISCUSSION Our findings will provide more evidence for the effects of hip abductor strengthening on relieving pain and improving function in KOA patients. Hip abductor strengthening can be added into the muscle training program for KOA patients as a supplementary content if it is proved to be effective. TRIAL REGISTRATION The current study has been registered with the Chinese Clinical Trials Registry (the registration number is ChiCTR-IOC-15007590 , 3rd December, 2015).
Hemobilia caused by pancreatic arteriovenous malformation: A case report and literature review.
RATIONALE Hemobilia caused by arteriovenous malformation is extremely rare but could be lethal. To date, most reports have been single-case reports, and no literature reviews are available. PATIENT CONCERNS A 47-year-old man presented to the emergency department with abdominal pain and fever. He complained of abdominal pain and weight loss for the past 2 months. DIAGNOSES Contrast-enhanced computed tomography and magnetic resonance imaging showed a heterogenous lesion located in pancreatic head and tumor was suspected. INTERVENTIONS Endoscopic retrograde cholangiopancreatography was performed and bleeding from papilla of Vater could be viewed. Nasobiliary drainage was placed to alleviate the pain and jaundice. Emergency laparotomy was performed due to the recurrence of severe pain and bleeding, and pancreatoduodenectomy was then performed. Macroscopic examination showed the ulceration connected with collected vessels which were located in pancreatic head and microscopic examination confirmed the presence of arteriovenous malformation. OUTCOMES The patient recovered uneventfully and was discharged 10 days after the surgery. He is asymptomatic on 4-month follow up. LESSONS Arteriovenous malformation is a rare cause of hemobilia, but it could lead to life threatening bleeding. Transarterial embolization could be effective to control the bleeding temporarily, however repeated hemorrhage may occur. Surgical resection may be a better option.
Impact of metoprolol treatment on cardiac function and exercise tolerance in heart failure patients with neuropsychiatric disorders.
Current medical research and opinion. 2018;(1):141-148
OBJECTIVE To investigate the impact of neuropsychiatric disorders on the effect of metoprolol on cardiac and motor function in chronic heart failure (CHF) patients. METHODS From February 2013 to April 2016, CHF patients with clinical mental disorders received metoprolol (23.75 or 47.5 mg, once daily, orally) at the Second Affiliated Hospital of Kunming Medical University. Mental status was confirmed by means of the Hospital Anxiety and Depression Scale (HADS) and the Copenhagen Burnout Inventory (CBI) scale. Cardiac function parameters such as systolic blood pressure (SBP), ejection fraction (EF) and cardiac index (CI) as well as motor function including the 6 meter walk test (6MWT) and the Veteran's Specific Activity Questionnaire (VSAQ) were assessed as primary outcomes of the study. RESULTS A total of 154 patients (median age, 66.39 years; men, n = 101) were allocated into eight groups based on their mental status. There were no significant differences in heart rate (HR) or SBP control achieved by metoprolol in any groups compared with the control (patients with normal mental status). Furthermore, biphasic ejection fraction (EF) changes were observed in all the groups with a decrease in the first month and increase from the sixth month. However, this increase was significantly lower (p < .001) than the EF achieved with metoprolol treatment in the control group except for the anxiety group. A similar pattern was seen for CI, 6MWT and VSAQ changes in all the groups. Patients in the anxiety group responded similarly to the patients with normal mental status. CONCLUSION Depressive and high burnout symptoms, but not anxiety, lower the improvement of cardiac and motor function by metoprolol treatment in CHF.
A 68-Year-Old Lung Transplant Recipient With Shortness of Breath, Weight Loss, and Abnormal Chest CT.
CASE PRESENTATION A 68-year-old man presented to our ED with shortness of breath, weakness, and a 25-lb unintentional weight loss. He had undergone bilateral lung transplantation (cytomegalovirus [CMV]: donor+, recipient+; Epstein-Barr virus: donor+; recipient+) for idiopathic pulmonary fibrosis (IPF) 18 months prior. His posttransplant course was fairly unremarkable until 1 month earlier, when he was admitted for breathlessness and weakness. CT of the chest during that admission revealed mild intralobular and interlobular septal thickening. A bronchoscopy with BAL and transbronchial biopsies did not show acute cellular rejection, but the BAL fluid was positive for coronavirus. His cortisol level was undetectable; he was diagnosed with adrenal insufficiency and fludrocortisone was initiated. He was taking prednisone, tacrolimus, and everolimus for immunosuppression and valganciclovir, itraconazole, and trimethoprim-sulfamethoxazole for antimicrobial prophylaxis. His 25-lb weight loss occurred over the span of just one month.
Successful second allogeneic stem-cell transplantation from the same sibling donor for a patient with recurrent hepatosplenic gamma-delta (γ/δ) T-cell lymphoma: A case report.
RATIONALE Hepatosplenic T-cell lymphoma (HSTCL) is a rare but aggressive type of peripheral T-cell lymphoma (PTCL). There is an urgent need for effective treatment due to the poor prognosis of HSTCL. Here, for the 1st time we describe the rare successful case of HSTCL who relapsed after a previous allogeneic stem-cell transplantation (allo-SCT), achieved remission with the second allo-SCT from the same donor. PATIENT CONCERNS A 24-year-old male, presented with a 2-week history of fever, drenching night sweats and nonquantified weight loss. DIAGNOSES Laboratory studies, flow cytometry of immunophenotyped, and physical examination results strongly suggested hepatosplenic γ/δ T-cell lymphoma, stage IVB. INTERVENTIONS We proceeded to an allo-SCT with a human leukocyte antigen (HLA) identical sibling donor. The bone marrow examination and fluorescent in situ hybridization were observed for complete donor chimerism of bone marrow cells on day 34. On day 157 after the initial allo-SCT, the bone marrow examination revealed the relapse of the sinusoidal infiltration with lymphoma cells. Considering the disease persistence, we conducted the second allo-SCT from the same HLA-identical sibling donor immediately. OUTCOMES Bone marrow examination indicated hematologic recovery without residual lymphoma cells. LESSONS Our encouraging outcome suggests that the latter allo-SCT needs to be considered early for patients with disease recurrence, and it also demonstrates that graft-vs-lymphoma conferred by allo-SCT may play an essential role on HSTCL treatment. Furthermore, detecting related genes at diagnosis may have prognostic implications and guidance value for personal chemotherapy program.