Efficiency Evaluation of Neuroprotection for Therapeutic Hypothermia to Neonatal Hypoxic-Ischemic Encephalopathy

Background: To evaluate the safety and neurological outcomes of therapeutic hypothermia to neonatal hypoxic-ischemic encephalopathy (HIE).Materials and Methods: Medical records of 61 neonates with moderate to severe HIE were retrospectively enrolled and divided into a therapeutic hypothermia group (n = 36) and conventional therapy group (n = 25).Results: No significant difference in the incidence of severe adverse events was found between the two groups. Minimum and maximum voltages of amplitude-integrated electroencephalography (aEEG) recording results showed statistically significant differences in therapeutic hypothermia group after 72 h. The neonatal behavioral neurological assessment (NBNA) on the 28th day after birth and Bayley Scales of Infant Development, second edition (BSID II) scores at 18 months old were significant higher in the therapeutic hypothermia group than the conventional therapy group.Conclusion: Therapeutic hypothermia for neonates with moderate to severe HIE improved the development of the nervous system in 0–18-month-old infants and showed a predominant role in reducing death and major neuron development-associated disabilities.

EFFECTIVENESS AND OUTCOMES OF H-ISDN IN ADDITION TO CONVENTIONAL THERAPY IN ACUTE HEART FAILURE PATIENTS WITH RENAL IMPAIRMENT

Objective:The primary objective of the study is todetermine whether the addition of H-ISDN to conventional therapy improves the cardiovascular outcomes and also to assess both short term(1 and 3 months) and long term outcomes(1 year). Materials and Methods:This is a prospective observational study.A total of 82 acute heart failure patients with renal impairment were divided into two groups based on exposure to H-ISDNGroup I-Patients on H-ISDN plus conventional therapyGroup II-Patients on conventional therapy. Followup of all the subjects to study the outcomes of improvement in NYHA class,rehospitalisation and mortality rate at 1 month,3 months and 1 year was done for both the groups. Results:We observed that out of the 82 acute heart failure patients with renal impairment,43 patients were receiving H-ISDN in addition to conventional therapy(Group I) and 39 patients were receiving conventional therapy(Group II) .The length of stay(6.03± 2.906 vs 6.93± 3.845) was shorter in the treated group when compared to the non treated group.A greater difference in reduced hospitalisation was seen at 3 months(2.32% vs 12.82%).The treated group had higher improvement in NYHA class at 1 month(67.44% vs 46.15%), 3 months(51.16% vs 41.02%) and 1 year (44.18% vs 20.51%P=0.023). Conclusion:Acute heart failure patients with renal impairment have poor prognosis. Randomised controlled trials are required to validate if the use of H-ISDN is associated with better outcomes in AHF patients.

IMMUNOLOGICAL ASSESSMENT OF THE STRESS RESPONSE IN PATIENTS WITH INFLAMMATORY POSTPROTHETIC COMPLICATIONS

Post-prosthetic complications during dental implantation are accompanied by pain symptoms leading to disorders of the psychoemotional state. All this influences the behavior of patients. In addition, psychoemotional stress is often a factor of provocation and persistence of the complications. The presence of a stress state in the identified pathology, as well as the influence of various therapies on the treatment of post-prosthetic complications, is reflected in the dynamics of changes in the concentrations of both catecholamines (epinephrine, norepinephrine) and glucocorticoids (cortisol) — hormones of the medulla and the adrenal cortex. The aim: to conduct an immunological analysis of the stress response in patients with postprosthetic complications during dental implantation. Materials and methods: The study was performed in 120 patients with post-prosthetic complications during dental implantation before and during treatment: Group I (control) — 30 patients treated with the conventional therapy; group II — 30 patients treated with ozone therapy in addition to the conventional therapy; group III — 30 patients treated with transcranial electrical stimulation in addition to the conventional therapy; Group IV — 30 patients treated with a combination of conventional therapy, ozone therapy and transcranial electrical stimulation. The concentration of epinephrine, norepinephrine, cortisol, alkaline phosphatase, and the Garkavi index were evaluated. Results: The change in these indicators after the treatment indicates the normalization of the level of the studied enzymes — markers of bone homeostasis, which is confirmed by an improvement in the clinical picture in the oral cavity. Conclusion: changes in immunological parameters objectively reflect the psychoemotional state of patients. The nature of changes in the hormonal stress response to the treatment of post-prosthetic complications indicates the effectiveness of the therapeutic regimens used, and, as a result, a decrease in both pain symptoms and psychoemotional stress.

Application Effect Evaluation of Telmisartan combined with Spironolactone after Catheter Ablation of Patients with Paroxysmal Atrial Fibrillation

Objective: To evaluate the application effect of telmisartan combined with spironolactone after catheter ablation of patients with paroxysmal atrial fibrillation. Methods: 80 cases of patients with paroxysmal atrial fibrillation who received radiofrequency catheter ablation treatment from March 2013 to March 2016 in our hospital were randomly selected, these patients were divided into two groups according to the treatment methods, namely, the telmisartan with Spironolactone treatment group (combined treatment group, n=40) and the conventional therapy group (n=40). The hs-CRP, NT-proBNP, LAD and recurrence of the two groups were analyzed. Results: The hs-CRP, NT-proBNP levels after 3 months of the combined treatment group were significantly lower (P<0.05), the recurrence rate 10.0% (4/40) was significantly lower than the conventional therapy group 27.5% (11/40) (P<0.05), the time to recurrence was significantly longer than the conventional therapy group (P<0.05). Conclusion: The application effects of telmisartan combined with spironolactone after catheter ablation in the treatment of patients with paroxysmal atrial fibrillation are better than conventional therapy.

Role of Darunavir/cobicisitat in the Treatment of COVID-19: Initial Virological and Clinical Findings

Background: COVID-19 still become a common threat to public health.In this study, we evaluated the antiviral effects and safety of darunavir/cobicisitat (DRV/c) in patients with confirmed COVID-19. Patients and Methods: Totally 66 patients with COVID-19 infection who were admitted to Zhongnan Hospital of Wuhan University between February 3 and March 11, 2020 were collected. The patients were divided into the DRV/c group and the control group. The Primary endpoints was the time of SARS-CoV-2 nucleic acid conversion detected in respiratory specimens.Results: A total of 66 subjects with confirmed SARS-CoV-2 infection were enrolled in this study, 32 subjects were enrolled in the DRV/c group and 34 in the control group. The mean time to nucleic acid conversion (NAC) was shorter in DRV/c group. The cumulative nucleic acid conversion rate (CNACR) in the DRV/C group was higher during the first 2 weeks, but the difference was not statistically significant. The proportion of fever during hospitalization in the DRV/C group was significantly lower than that in the control group (P value 0.01). It was found that in DRV/c group NAC of patients with duration from symptom onset to admission within 3 days was significantly shorter (7.9 ± 6.7 days) than that of and above 3 days (15.9 ± 7.1 days)( P = 0.01). Conclusion: Although the combination of DRV/c and routine treatment for patients with non-severe COVID-19 can significantly reduce the proportion of fever after admission, but no significant differences were observed between the DRV/c group and the conventional therapy group, including overall time to nucleic acid conversion, safety and tolerability.

Early Administration of Tolvaptan Can Improve Survival in Patients with Cirrhotic Ascites

(1) Backgrounds and aim: Tolvaptan, a selective vasopressin type 2 receptor antagonist, was approved for ascites, and its short-term efficacy and safety have been confirmed. However, it is still unclear whether this novel drug may improve long-term survival rates in cirrhotic patients with ascites. (2) Patients and methods: A total of 206 patients who responded insufficiently to conventional diuretics and were hospitalized for refractory ascites for the first time were retrospectively enrolled in this study. Among them, the first 57 consecutive patients were treated with conventional diuretics (the conventional therapy group); the latter 149 consecutive patients were treated with tolvaptan in addition to the conventional therapy (the tolvaptan group). (3) Results: The exacerbation of renal function was significantly milder in the tolvaptan group than in the conventional therapy group. The prognostic factors for survival in the tolvaptan group were being male, having hyperbilirubinemia, having a high blood urea nitrogen (BUN), and receiving high-dose furosemide at the start of tolvaptan treatment. The one-year and three-year cumulative survival rates were 67.8 and 45.3%, respectively, in patients with low-dose furosemide (<40 mg/day) at the start of tolvaptan treatment. The prognosis was significantly better in the tolvaptan group with low-dose furosemide than in the conventional therapy group (p < 0.001). (4) Conclusion: Tolvaptan can improve survival in patients with cirrhotic ascites, especially when tolvaptan is started before high-dose furosemide administration.

Therapeutic Effect of Perioperative Mild Hypothermia on Postoperative Neurological Outcomes in Patients with Acute Stanford Type A Aortic Dissection

Background: Postoperative patients of acute Stanford type A aortic dissection (AAAD) often experience complications consisting of nervous system injury. Mild hypothermia therapy has been proven to provide the therapeutic effect of cerebral protection. We aimed to investigate the therapeutic effects of perioperative mild hypothermia on postoperative neurological outcomes in patients with AAAD. Methods: A prospective randomized controlled study was conducted on adult patients undergoing aortic dissection surgery between February 2017 and December 2017. Patients in the treatment group underwent mild hypothermia (34° to 35°C) immediately after surgery, and in the conventional therapy group, patients were rewarmed to normal body temperature (36° to 37°C). Postoperative time to regain consciousness, postoperative serum neuron-specific enolase (NSE) and S-100β levels, cerebral tissue oxygen saturation, presence of delirium or permanent neurological dysfunction, intensive care unit (ICU) and hospital stay duration, and 28-day mortality were compared. Results: We enrolled 55 patients who underwent AAAD surgery and were randomly allocated into to 2 groups, 27 patients in the treatment group and 28 patients in the conventional therapy group. Compared with the conventional therapy group, postoperative time to regain consciousness was much shorter for patients in the mild hypothermia group (12.65 hours, interquartile range [IQR] 8.28 to 23.82, versus 25.80 hours, IQR 14.00 to 59.80; P = .02), and the rate of regaining consciousness in 24 hours after surgery was much higher (74.07% versus 46.42%; P = .037). At the same time, the ICU stay of patients in the mild hypothermia therapy group was significantly shorter than that in the conventional therapy group (5.53 ± 3.13 versus 9.35 ± 8.76 days; P = .038). Cerebral tissue oxygen saturation, incidence of delirium or permanent neurological dysfunction, duration of hospital stay, and 28-day mortality showed no statistical difference. Postoperative serum NSE and S-100β levels increased compared with preoperative baseline values in both groups (P < .05), and the serum NSE levels of patients in the mild hypothermia therapy was significantly lower than the conventional therapy group 1 hour (P = .049) and 6 hours (P = .04) after surgery. There was no difference in the chest drainage volume or shivering between the 2 groups 24 hours after surgery. Conclusions: Perioperative mild hypothermia therapy is able to significantly reduce brain cell injury and shorten the postoperative time to regain consciousness, thus improving the neurological prognosis of patients with AAAD.

Atorvastatin and Aspirin as Adjuvant Therapy in Patients with SARS-CoV-2 Infection: A structured summary of a study protocol for a randomised controlled trial

Objectives To assess the impact of adding statin (atorvastatin) and/or aspirin on clinical deterioration in patients infected with SARS-CoV-2 who require hospitalisation. The safety of these drugs in COVID-19 patients will also be evaluated. Trial design This is a single-centre, prospective, four-arm parallel design, open-label, randomized control trial. Participants The study will be conducted at National Cancer Institute (NCI), Jhajjar, Haryana, which is a part of All India Institute of Medical Sciences (AIIMS), New Delhi, and has been converted into a dedicated COVID-19 management centre since the outbreak of the pandemic. All RT-PCR confirmed cases of SARS-CoV-2 infection with age ≥ 40 years and < 75 years requiring hospital admission (patients with WHO clinical improvement ordinal score 3 to 5) will be included in the trial. Written informed consent will be taken for all recruited patients. Patients with a critical illness (WHO clinical improvement ordinal score > 5), documented significant liver disease/dysfunction (aspartate transaminase [AST] / alanine aminotransferase [ALT] > 240), myopathy and rhabdomyolysis (creatine phosphokinase [CPK] > 5x normal), allergy or intolerance to statins or aspirin, prior statin or aspirin use within 30 days, history of active gastrointestinal bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, or inability to take oral or nasogastric medications will be excluded. Patients refusing to give written consent and taking drugs that are known to have a significant drug interaction with statin or aspirin [including cyclosporine, HIV protease inhibitors, hepatitis C protease inhibitor, telaprevir, fibric acid derivatives (gemfibrozil), niacin, azole antifungals (itraconazole, ketoconazole), clarithromycin and colchicine] will also be excluded from the trial. Intervention and comparator In this study, the benefit and safety of atorvastatin (statin) and/or aspirin as adjuvant therapy will be compared with the control group receiving usual care for management of COVID-19. Atorvastatin will be prescribed as 40 mg oral tablets once daily for ten days or until discharge, whichever is earlier. The dose of aspirin will be 75 mg once daily for ten days or until discharge, whichever is earlier. All other therapies will be administered according to the institute’s COVID-19 treatment protocol and the treating physician’s clinical judgment. Main outcomes All study participants will be prospectively followed up for ten days or until hospital discharge, whichever is longer for outcomes. The primary outcome will be clinical deterioration characterized by progression to WHO clinical improvement ordinal score ≥ 6 (i.e., endotracheal intubation, non-invasive mechanical ventilation, pressor agents, renal replacement therapy, ECMO requirement, and mortality). The secondary outcomes will be change in serum inflammatory markers (C-reactive protein and Interleukin-6), Troponin I, and creatine phosphokinase (CPK) from time zero to 5th day of study enrolment or 7th day after symptom onset, whichever is later. Other clinical outcomes that will be assessed include progression to Acute Respiratory Distress Syndrome (ARDS), shock, ICU admission, length of ICU admission, length of hospital admission, and in-hospital mortality. Adverse drug effects like myalgia, myopathy, rhabdomyolysis, hepatotoxicity, and bleeding will also be examined in the trial to assess the safety of the interventions. Randomisation The study will use a four-arm parallel-group design. A computer-generated permuted block randomization with mixed block size will be used to randomize the participants in a 1:1:1:1 ratio to group A (atorvastatin with conventional therapy), group B (aspirin with conventional therapy), group C (aspirin + atorvastatin with conventional therapy), and group D (control; only conventional therapy). Blinding (masking) The study will be an open-label trial. Numbers to be randomised (sample size) As there is no existing study that has evaluated the role of aspirin and atorvastatin in COVID-19 patients, formal sample size calculation has not been done. Patients satisfying the inclusion and exclusion criteria will be recruited during six months of study period. Once the first 200 patients are included in each arm (i.e., total 800 patients), the final sample size calculation will be done on the basis of the interim analysis of the collected data. Trial Status The institutional ethical committee has approved the study protocol (Protocol version 3.0 [June 2020]). Participant recruitment starting date: 28th July 2020 Participant recruitment ending date: 27th January 2021 Trial duration: 6 months Trial registration The trial has been prospectively registered in Clinical Trial Registry – India (ICMR- NIMS): Reference no. CTRI/2020/07/026791 (registered on 25 July 2020)]. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Effect of ticagrelor monotherapy on mortality after percutaneous coronary intervention: a systematic review and meta-analysis of randomized trials including 26 143 patients

Aims Optimal timing and strategy of antiplatelet monotherapy after dual-antiplatelet therapy (DAPT) consisting of aspirin and P2Y12 inhibitor for patients who underwent percutaneous coronary intervention (PCI) is still being debated. The aim of this study was to evaluate the effect of ticagrelor monotherapy after short-term DAPT after PCI on mortality. Methods and results A systematic review and meta-analysis was performed using PubMed to search for ticagrelor monotherapy after short-term DAPT comparing conventional DAPT in patients who underwent PCI. Three randomized trials encompassing 26 143 patients [ticagrelor monotherapy after 1–3 months of DAPT (n = 13 062) vs. conventional therapy (n = 13 081)] were included. The efficacy endpoint of all-cause mortality was significantly lower with the ticagrelor monotherapy group vs. the conventional therapy group [risk ratio (RR) = 0.80, 95% confidence interval (CI) 0.65–0.98; P = 0.03; I2 = 0%; number needed to treat for benefit (NNTB) = 320]. The safety endpoint of Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding was also significantly lower with the ticagrelor monotherapy group vs. the conventional therapy group (RR = 0.67, 95% CI 0.49–0.92; P = 0.01; I2 = 65%; NNTB = 156). There were no significant differences in ischaemic stroke, acute myocardial infarction, and stent thrombosis. The favourable effects of the ticagrelor monotherapy vs. the conventional therapy on all-cause mortality and BARC type 3 or 5 bleeding were consistent in the subset of patients presenting acute coronary syndromes (n = 15 157). Conclusion Ticagrelor monotherapy after short-term DAPT of 1–3 months was associated with decreased all-cause mortality and BARC type 3 or 5 bleeding not offset by increase of cardiac death, ischaemic stroke, acute myocardial infarction, and stent thrombosis.

Nafamostat Mesylate Improved Survival Outcomes of Sepsis Patients Who Underwent Blood Purification: A Nationwide Registry Study in Japan

Nafamostat mesylate (NM) is a synthetic serine protease inhibitor that can be used as an anticoagulant during blood purification in critically ill patients, as well as a treatment for disseminated intravascular coagulation. Although NM has been reported to reduce the risk of bleeding during blood purification, its effect on survival outcomes of patients who received blood purification treatments is unclear. We hypothesized that administration of NM during blood purification can reduce mortality in patients with sepsis. A post hoc analysis was conducted on a nationwide retrospective registry that included data from 3195 sepsis patients registered at 42 intensive care units throughout Japan. We evaluated the effect of NM on hospital mortality and bleeding complications using propensity score matching in 1216 sepsis patients who underwent blood purification in the intensive care unit (ICU). Two-hundred-and-sixty-eight pairs of propensity score-matched patients who received NM and conventional therapy were compared. Hospital and ICU mortality rates in the NM group were significantly lower than those in the conventional therapy group. However, rates of bleeding complications did not differ significantly between the two groups. These data suggest that administration of NM improved the survival outcomes of sepsis patients who underwent blood purification in the ICU.