The newest virus from the SARS family of viruses called acute syndrome-coronavirus-2 (SARS-CoV-2), which causes COVID-19 disease, was identified in China at the end of 2019. In March 2020, after it spread to 29 additional countries, it was declared a pandemic by the World Health Organization (WHO). SARS-CoV-2 infection mainly starts through the respiratory tract and causes a wide spectrum of symptoms from asymptomatic infections to acute respiratory distress syndrome with multi-organ failure and vasoplegic shock. Among the many immunomodulatory and antiviral drugs that have been studied for the treatment of COVID-19, methylene blue (MB) may play an influential role. This article reviews the history of MB applications, the antiviral effects of MB against SARS-CoV-2, and the results of in vivo and in vitro studies of the use of MB in COVID-19. Based on studies, MB can simultaneously affect most of the host\'s harmful responses caused by SARS-CoV-2 infection due to its multiple properties, including anti-hypoxemia, anti-oxidant, immune system modulator, and antiviral. The use of MB is associated with a reduction in the possibility of getting infection, and mortality, and can be used as a safe, effective, cheap, and available treatment option with minimal side effects for the clinical management of COVID-19.

The newest virus from the SARS family of viruses called acute syndrome-coronavirus-2 (SARS-CoV-2), which causes COVID-19 disease, was identified in China at the end of 2019. In March 2020, after it spread to 29 additional countries, it was declared a pandemic by the World Health Organization (WHO). SARS-CoV-2 infection mainly starts through the respiratory tract and causes a wide spectrum of symptoms from asymptomatic infections to acute respiratory distress syndrome with multi-organ failure and vasoplegic shock. Among the many immunomodulatory and antiviral drugs that have been studied for the treatment of COVID-19, methylene blue (MB) may play an influential role. This article reviews the history of MB applications, the antiviral effects of MB against SARS-CoV-2, and the results of in vivo and in vitro studies of the use of MB in COVID-19. Based on studies, MB can simultaneously affect most of the host\'s harmful responses caused by SARS-CoV-2 infection due to its multiple properties, including anti-hypoxemia, anti-oxidant, immune system modulator, and antiviral. The use of MB is associated with a reduction in the possibility of getting infection, and mortality, and can be used as a safe, effective, cheap, and available treatment option with minimal side effects for the clinical management of COVID-19.

UNASSIGNED: Subthalamic nucleus (STN) and globus pallidus interna (GPi) are two main structures primarily targeted by deep brain stimulation (DBS) to treat advanced Parkinson\'s disease (PD). A subset of cases with unsatisfactory outcomes may benefit from rescue DBS surgery targeting another structure, while these patients\' characteristics have not been well described and this phenomenon has not been well reviewed.
UNASSIGNED: This monocentric retrospective study included patients with PD, who underwent rescue STN DBS following an unsatisfactory outcome of the initial bilateral GPi DBS in a retrospective manner. A short review of the current literature was conducted to report the clinical outcome of rescue DBS surgeries.
UNASSIGNED: Eight patients were identified, and six of them were included in this study. The rescue STN DBS was performed 19.8 months after the initial GPi DBS. After 8.8 months from the rescue STN DBS, patients showed a significant off-medication improvement by 29.2% in motor symptoms compared to initial GPi DBS. Non-motor symptoms and the health-related quality of life were also significantly improved.
UNASSIGNED: Our findings suggest that the rescue STN DBS may improve off-medication motor and non-motor symptoms and quality of life in patients with failure of initial GPi DBS. The short review of the current literature showed that the target switching from GPi to STN was mainly due to poor initial outcomes and was performed by target substitution, whereas the switching from STN to GPi was mainly due to a gradual waning of benefits, long-term axial symptoms, dyskinesia, and dystonia and was performed by target addition.

In this review article, we summarized the current advances in rescue management for reperfusion therapy of acute ischemic stroke from large vessel occlusion due to underlying intracranial atherosclerotic stenosis (ICAS). It is estimated that 24-47% of patients with acute vertebrobasilar artery occlusion have underlying ICAS and superimposed in situ thrombosis. These patients have been found to have longer procedure times, lower recanalization rates, higher rates of reocclusion and lower rates of favorable outcomes than patients with embolic occlusion. Here, we discuss the most recent literature regarding the use of glycoprotein IIb/IIIa inhibitors, angioplasty alone, or angioplasty with stenting for rescue therapy in the setting of failed recanalization or instant/imminent reocclusion during thrombectomy. We also present a case of rescue therapy post intravenous tPA and thrombectomy with intra-arterial tirofiban and balloon angioplasty followed by oral dual antiplatelet therapy in a patient with dominant vertebral artery occlusion due to ICAS. Based on the available literature data, we conclude that glycoprotein IIb/IIIa is a reasonably safe and effective rescue therapy for patients who have had a failed thrombectomy or have residual severe intracranial stenosis. Balloon angioplasty and/or stenting may be helpful as a rescue treatment for patients who have had a failed thrombectomy or are at risk of reocclusion. The effectiveness of immediate stenting for residual stenosis after successful thrombectomy is still uncertain. Rescue therapy does not appear to increase the risk of sICH. Randomized controlled trials are warranted to prove the efficacy of rescue therapy.

BACKGROUND: Due to increasing resistance rates of Helicobacter pylori (H. pylori) to different antibiotics, failures in eradication therapies are becoming more frequent. Even though eradication criteria and treatment algorithms for first-line and second-line therapy against H. pylori infection are well-established, there is no clear recommendation for third-line and rescue therapy in refractory H. pylori infection.
OBJECTIVE: To perform a systematic review evaluating the efficacy and safety of rescue therapies against refractory H. pylori infection.
METHODS: A systematic search of available rescue treatments for refractory H. pylori infection was conducted on the National Library of Medicine\'s PubMed search platform based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or non-randomized clinical trials and observational studies evaluating the effectiveness of H. pylori infection rescue therapies were included.
RESULTS: Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy, and 21 of these were selected for analysis of mean eradication rate as third-line treatment. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple-therapy as third-line treatment, mean eradication rates of 81.6% and 84.4%, 79.4% and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in intention-to-treat (ITT) and per-protocol (PP) analysis, respectively. For third-line quadruple therapy, mean eradication rates of 69.2% and 72.1% were found for bismuth quadruple therapy (BQT), 88.9% and 90.9% for bismuth quadruple therapy, three-in-one, Pylera® (BQT-Pylera), and 61.3% and 64.2% for non-BQT) in ITT and PP analysis, respectively. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple therapy as rescue therapy, mean eradication rates of 75.4% and 78.8%, 79.4 and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in ITT and PP analysis, respectively. For quadruple therapy as rescue treatment, mean eradication rates of 76.7% and 79.2% for BQT, 84.9% and 87.8% for BQT-Pylera, and 61.3% and 64.2% for non-BQT were found in ITT and PP analysis, respectively. For susceptibility-guided therapy, mean eradication rates as third-line and rescue treatment were 75.0% in ITT and 79.2% in PP analysis.
CONCLUSIONS: We recommend sitafloxacin-based triple therapy containing vonoprazan in regions with low macrolide resistance profile. In regions with known resistance to macrolides or unavailability of bismuth, rifabutin-based triple therapy is recommended.

The changes in the serum levels of aquaporin-4-IgG (AQP4-IgG), immunoglobulins, and inflammatory mediators in neuromyelitis optica spectrum disorder (NMOSD) cases treated with immunoadsorption have been rarely described in detail. Here we report a 29-year-old steroid-resistant NMOSD female with a severe disability (bilateral blindness and paraplegia) who received protein-A immunoadsorption as a rescue treatment. During the total 5 sessions, the circulating level of AQP4-IgG, immunoglobulins, and complement proteins (C3 and C4) showed a rapid and sawtooth-like decrease, and the serum AQP4-IgG titer declined from 1:320 to below the detectable limit at the end of the 3rd procedure. Of all the antibodies, IgG had the biggest removal rate (>96.1%), followed by IgM (>66.7%) and IgA (53%), while complement C3 and C4 also dropped by 73% and 65%, respectively. The reduced pro-inflammatory cytokines (interleukin-8 and tumor necrosis factor-α) and marked increased lymphocyte (T and B cell) counts were also observed. The improvement of symptoms initiated after the last session, with a low AQP4-IgG titer (1:32) persisting thereafter. Accordingly, protein-A immunoadsorption treatment could be one of the potential rescue therapies for steroid-resistant NMOSD patients with a severe disability.

Benzodiazepines such as diazepam, lorazepam and midazolam remained the mainstay of treatment for acute repetitive seizures (ARS). The immediate care for ARS should often begin at home by a caregiver. This prevents the progression of ARS to prolonged seizures or status epilepticus. For a long time and despite social objections rectal diazepam gel remained only FDA-approved rescue medication. Intranasal administration of benzodiazepines is considered attractive and safe compared with rectal, buccal and sublingual routes. Intranasal delivery offers numerous advantages such as large absorptive surface area, bypass the first-pass metabolism and good patient acceptance as it is needle free and painless. Recent clinical studies have demonstrated that diazepam nasal spray (NRL-1; Valtoco®, Neurelis Inc.,San Diego, CA, USA) showed less pharmacokinetic variability and reliable bioavailability compared with the diazepam rectal gel. Diazepam nasal spray could be considered as a suitable alternative for treating seizure emergencies outside the hospital. This review summarizes the treatment options for ARS and findings from clinical studies involving intranasal diazepam for treating seizure emergencies.

BACKGROUND: Despite randomized controlled trials [RCTs] and trial-based meta-analyses, the optimal rescue therapy for patients with acute glucorticosteroid-refractory ulcerative colitis [UC], to avoid colectomy and improve long-term outcomes, remains unclear. We conducted a network meta-analysis examining this issue.
METHODS: We searched MEDLINE, EMBASE, EMBASE Classic and the Cochrane central register up to June 2020. We included RCTs comparing ciclosporin and infliximab, either with each other or with placebo, in patients with glucorticosteroid-refractory UC.
RESULTS: We identified seven RCTs containing 534 patients [415 in head-to-head trials of ciclosporin vs infliximab]. Risk of colectomy at ≤ 1 month was reduced significantly with both treatments, compared with placebo (relative risk [RR] of colectomy with infliximab vs placebo = 0.37; 95% confidence interval [CI] 0.21-0.65, RR with ciclosporin vs placebo = 0.40; 95% CI 0.21-0.77). In terms of colectomy between > 1 month and < 1 year, both drugs ranked equally [P-score 0.75]. Neither treatment was more effective than placebo in reducing the risk of colectomy at ≥ 1 year. Both ciclosporin and infliximab were significantly more efficacious than placebo in achieving a response. Neither treatment was more effective than placebo in inducing remission, nor more likely to cause serious adverse events than placebo.
CONCLUSIONS: Both ciclosporin and infliximab were superior to placebo in terms of response to therapy and avoiding colectomy up to 1 year, with no significant differences in efficacy or safety between the two. Ciclosporin remains a valid option to treat refractory UC patients, especially those who do not respond to previous treatment with infliximab, or as a bridge to other biological therapies.

OBJECTIVE: To evaluate the efficacy and safety of endovascular treatment (ET) of acute ischemic stroke (AIS) caused by intracranial atherosclerotic large vessel occlusion (ICAS-LVO).
METHODS: A systemic review and meta-analysis were conducted on studies published between July 2005 and October 2018 on the outcomes of ET in patients with AIS due to ICAS-LVO. The outcomes of the ICAS-LVO and embolic LVO groups were also compared.
RESULTS: A total of 17 studies including 1315 subjects with ICAS-LVO were included. In the single-arm meta-analysis, the pooled estimates of successful recanalization rate, favorable outcomes, symptomatic intracranial hemorrhage and mortality were 88% (95% CI (95% confidence interval), 84-92%), 52% (95% CI, 47-56%), 5% (95% CI, 3-7%) and 15% (95% CI, 12-19%) respectively. The preferred primary treatment was stent-retriever thrombectomy (84.1%) and the preferred rescue treatment was stent implantation with or without percutaneous transluminal angioplasty (PTA, 32.7%). In the double-arm meta-analysis, the incidence of symptomatic intracranial hemorrhage was lower in the ICAS-LVO compared to the embolic-LVO group (OR (odds ratio) = 0.60, 95% CI, 0.46-0.77, p < 0.01), whereas the implementation of rescue treatment (OR = 5.94, 95% CI, 3.15-11.19, p < 0.01) and stenting rate (OR = 10.06, 95%CI, 4.43-22.85, p < 0.01) were higher in the ICAS-LVO group. Other parameters were similar in both groups.
CONCLUSIONS: The use of ET is a safe and effective therapeutic option for AIS due to ICAS-LVO. Stent-retriever thrombectomy and stent-implement are the preferred primary and rescue therapies respectively for ICAS-LVO. Less symptomatic intracranial hemorrhage and higher stenting were observed in the ICAS-LVO compared to the embolic-LVO group.

Pharmacokinetic data suggest that standard induction dosing schedules may not be sufficient in patients with acute severe colitis (ASUC). Hence, intensified induction regimes are increasingly used in the rescue treatment of hospitalized patients with ASUC to avoid the need for colectomy although the evidence for this is uncertain.
To conduct a systematic review of short- and long-term efficacy outcomes from accelerated infliximab induction studies.
Systematic search of relevant databases (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews) and relevant conference proceedings (Digestive Diseases Week, European Colitis and Crohn\'s Organisation Congress, United European Gastroenterology Week) was done.
We identified ten relevant studies with a total of 705 patients, of whom 308 received an intensified infliximab regime. Pooled analysis showed no difference in short-term or long-term colectomy rates in those receiving accelerated induction regimes when compared to standard induction. No significant differences in complication rates were identified.
The available uncontrolled studies so far do not suggest short-term or long-term benefit in using accelerated induction in hospitalized ASUC. The overall poor quality of available studies with confounding variables indicates the need for a randomized controlled trial with personalized risk stratification.