Acute Severe Ulcerative Colitis (ASUC) is a severe form of ulcerative colitis relapse which requires hospitalization and intensive medical intervention to avoid colectomy. The timely recognition of patients at risk of corticosteroid failure and the early initiation of medical rescue therapy are paramount in the management of ASUC. The choice of medical rescue therapy is influenced by multiple factors, especially patient\'s prior treatment history. This decision should involve the patient and ideally a multidisciplinary team of healthcare professionals, including gastroenterologists, radiologists, surgeons and enterostomal therapists. Although several predictive models have been developed to predict corticosteroid failure in ASUC, there is no single validated tool that is universally utilized. At present, infliximab and cyclosporine are the only agents systematically evaluated and recommended for medical rescue therapy, with recent reports of off-label utilization of tofacitinib and upadacitinib in small case series. The available evidence regarding the efficacy and safety of these oral small molecules for ASUC is insufficient to provide definitive recommendations. Early decision-making to assess the response to medical rescue therapy is essential, and the decision to pursue surgery in the case of treatment failure should not be delayed.

Eculizumab has improved recovery from ventilatory support in myasthenic crisis (MC) cases. However, the safety and efficacy profiles from prospective studies are still lacking. This study aimed to explore eculizumab\'s safety and efficacy in a prospective case series of patients with refractory MC. We followed a series of anti-acetylcholine receptor (AChR) antibody-positive myasthenia gravis (MG) patients who received eculizumab as an add-on therapy for 12 weeks during MC to facilitate the weaning process and reduced disease activity. Serum anti-AChR antibodies and peripheral immune molecules associated with the complement pathway were evaluated before and after eculizumab administration. Compared to the baseline Myasthenia Gravis Foundation of America (MGFA)-quantitative MG test (QMG) scores (22.25 ± 4.92) and MG-activities of daily living (MG-ADL; 18.25 ± 2.5) scores at crisis, improvements were observed from 4 weeks (14.5 ± 10.47 and 7.5 ± 7.59, respectively) through 12 weeks (7.5 ± 5.74 and 2.25 ± 3.86, respectively) post-treatment. Muscle strength consistently improved across ocular, bulbar, respiratory, and limb/gross domain groups. One patient died of cardiac failure at 16 weeks. Three cases remained in remission at 24 weeks, with a mean QMG score of 2.67 ± 2.89 and ADL score of 0.33 ± 0.58. No significant side effects were reported. Serum CH50 and soluble C5b-9 levels significantly declined, while there were no significant changes in serum anti-AChR antibody levels, C1q, C5a levels, or peripheral lymphocyte proportions. Eculizumab was well tolerated and showed efficacy in this case series. Large prospective cohort studies with extended follow-up periods are needed to further explore the safety and efficacy profile in real-world practice.

BACKGROUND: To evaluate the anatomical and functional outcomes of high-density subthreshold micropulse laser (HSML) treatment in a cohort of patients diagnosed with chronic central serous chorioretinopathy (CSCR) whose treatment with photodynamic therapy (PDT) was delayed due to the worldwide shortage of verteporfin.
METHODS: Prospective interventional study which included 42 eyes of 40 patients diagnosed with chronic CSCR and on the waiting list for PDT who received rescue therapy with HSML using the Navilas® System device (OD-OS GmBH, Teltwo, Germany). Best corrected visual acuity (BCVA), subretinal fluid (SRF), and subfoveal choroidal thickness (SFCT) were measured at inclusion and during the follow-up visits at 2, 4, and 6 months.
RESULTS: The mean waiting time from the indication of PDT until treatment with HSML was 14.6 ±9.7 months (range 5-21). There were no differences in the pre-treatment BCVA compared with the 6-month follow-up visit (67 ±16.7 letters and 67.5 ±8.2 letters respectively, p=0.136). However, there was a significant decrease in the mean SFCT of -39.6 ±37.1 μm (p=0.030). Additionally, there was a decrease in SRF height between the pre-treatment measure (123.0 ±49.8 μm) and the 2, 4, and 6-month follow-up visits after HSML of -58.5 ±68.2 μm, -53.2 ±76.3 μm, and -65.4 ±53.6 μm respectively (p<0.001). A complete resolution of the SRF was observed in 16/42 eyes (38.1%) and a reduction of the SRF height in 85.7% of the overall cohort was observed after HSML treatment.
CONCLUSIONS: A significant anatomical improvement in SRF and a decrease in SFCT were observed in patients with CSCR who were previously waiting for PDT and were rescued by HSML. However, the rate of complete SRF resolution was low.

BACKGROUND: Therapeutic plasma exchange (TPE) is a highly effective rescue treatment for patients with acute exacerbation of neuroimmunological disease that removes circulating autoantibodies and inflammatory components from the bloodstream. The aims of this study are to explore the safety and the effectiveness of TPE in patients with autoimmune neurological disorders.
METHODS: We retrospectively evaluated the frequency of adverse events (AEs) and the effectiveness of TPE using the modified Ranking Scale (mRS) in patients with acute neurological flares who underwent TPE at the University Hospital of Palermo.
RESULTS: Of 59 patients, the majority underwent TPE due to multiple sclerosis (MS) relapse. In 23.7% of cases, TPE was performed before obtaining a definite diagnosis due to the severity of the clinical presentation. After TPE, the mRS score was globally reduced (p < 0.0001), and this effect was marked in patients with MS, Guillain-Barré syndrome, and myasthenia gravis crisis but not in those with paraneoplastic syndromes. Circulating pathogenetic antibodies, younger age, and the early use of TPE were factors strongly associated with TPE effectiveness. The overall safety profile of TPE was satisfactory with an AE frequency of 15%.
CONCLUSIONS: These results highlight the early use of TPE in patients with circulating pathogenetic antibodies as well as its favorable safety profile.

UNASSIGNED: Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. ‍This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries.
UNASSIGNED: A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients.
UNASSIGNED: Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively.
UNASSIGNED: Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.

OBJECTIVE: Approximately 40% of patients with steroid-refractory acute severe ulcerative colitis (steroid-refractory (SR) ASUC) requires colectomies. Advanced therapies may reduce the short-term colectomy rates in patients with SR ASUC. However, comparative clinical studies evaluating the effectiveness of these rescue therapies are lacking. Therefore, we conducted a network meta-analysis to study the effectiveness of rescue therapies for SR ASUC.
METHODS: Six randomized controlled trials and 15 cohort studies including 2,004 patients were analyzed. Rescue drugs included tofacitinib, infliximab with a 5 or 10 mg/kg induction dose at 0, 2, and 6 weeks (IFX and IFX10, respectively), IFX with an accelerated regimen of three 5 mg/kg induction doses timed according to clinical need (accelerated IFX), tacrolimus, cyclosporine (CyA), ustekinumab, and adalimumab. Treatments were compared with a placebo.
RESULTS: Tofacitinib (odds ratio [OR]: 0.09 [95% confidence interval [CI]: 0.02-0.52]), accelerated IFX (OR: 0.16 [95% CI: 0.03-0.94]), IFX (OR: 0.2 [95% CI: 0.07-0.58]), and tacrolimus (OR: 0.24 [95% CI: 0.06-0.96]) significantly reduced the short-term colectomy rates compared with placebo. IFX10 and CyA tended to prevent colectomies. However, ustekinumab and adalimumab did not significantly affect the colectomy rates.
CONCLUSIONS: This is the first network meta-analysis to investigate the efficacy of advanced therapies in reducing short-term colectomy rates in patients with SR ASUC. Tofacitinib, accelerated IFX, standard IFX, and tacrolimus significantly reduced the colectomy rates in SR ASUC patients compared with placebo. Thus, advanced therapies should be considered for rescue therapies in patients with SR ASUC.

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OBJECTIVE: This review aims to assess the therapeutic strategies available for relapsed/refractory patients with immunoglobulin light chain (AL) amyloidosis who received upfront daratumumab-based regimens.
RESULTS: The treatment landscape of AL amyloidosis has changed radically thanks to the introduction in the upfront setting of daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone (DaraCyBorD) which improved patients\' outcomes increasing the rate of hematologic and organ responses. However, many patients eventually relapse or are refractory to daratumumab and the best salvage therapy is not well defined yet. In this contest, we reviewed the available therapeutic options after daratumumab failure, and we look towards the current advances in Bcl-2 inhibitors, novel immunotherapeutic agents as chimeric antigen receptor (CAR-T) therapy and bispecific antibodies (bsAbs). Relapsed/refractory AL amyloidosis represent an unmet clinical need and novel targeted drugs require urgent prospective assessment.

Diazepam is a cornerstone immediate-use antiseizure rescue therapy that may extend the duration between seizure clusters in people living with epilepsy. However, our mechanistic understanding of intermittent rescue therapy on disease progression is limited by the lack of suitable preclinical models. Specifically, the pharmacokinetics of diazepam varies widely between humans and laboratory animals. Here, we developed a novel repeat rescue therapy dosing paradigm in rats to maintain prolonged therapeutic concentrations seen in humans. Rats received three diazepam doses separated by 1 h (0.75, 1.5, or 3 mg/kg, intraperitoneal); plasma and brains were collected at 10 min and 1, 3, or 6 h following the last dose. Plasma and brain concentrations followed a dose-dependent increase with peak concentrations following the repeat 3 mg/kg paradigm (180 ng/mL) being equivalent to plasma levels observed in human studies with diazepam nasal spray. Increased brain-to-plasma ratios in this paradigm indicate that diazepam accumulation in the brain may be long-acting at the site of action. Overall, our repeat diazepam dosing paradigm mimics drug concentrations and accumulation seen in humans, offering a preclinical tool to study the impact of benzodiazepine rescue therapy on seizure-cluster biology in rodent models of epilepsy. PLAIN LANGUAGE SUMMARY: There is more to learn about how diazepam works in the brains of people who use it only when they have two or more seizures in 24 h (this is called a seizure cluster). Ethical studies in animals can be used to learn more about medicines in the body. In this study, we showed that three doses of diazepam in rats give about the same amount of the drug as one dose for a person. We can now test rats with epilepsy to see how the drug might work in people who take it when needed for seizure clusters.

UNASSIGNED: Neurologic circadian influences, including sleep/wake transitions, processes (e.g., hormonal variation), and behavioral patterns (e.g., consumption of food and oral medications), may affect seizure patterns. Specific circadian patterns of seizures have been reported depending on type, onset location, and severity; however, data on patterns for patients with seizure clusters and effectiveness of rescue therapy by time of day are limited.
UNASSIGNED: We conducted post hoc analyses using patient diary data from the phase 3 safety study of diazepam nasal spray, which is indicated for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Patients were administered age- and weight-based doses; second doses could be administered if needed to control a seizure cluster. We assessed clock timing of seizure-cluster onset along with second-dose use as a proxy for effectiveness. Treatment-emergent adverse events were recorded.
UNASSIGNED: Seizure-cluster onset was observed to be generally highest during mornings and late evenings and lowest in the early evening and middle of the night. Second-dose use was not consistently associated with a specific time of day. The safety profile was consistent with that expected from previous studies of diazepam nasal spray.
UNASSIGNED: These results suggest that diazepam nasal spray can be effectively administered at any time of day.