[Clinical observation on acupuncture at infusion points of "four seas" on refractory peripheral facial paralysis].

OBJECTIVE: To observe the clinical effect of acupuncture at the infusion points of "four seas" for refractory peripheral facial paralysis on the basis of conventional acupuncture. METHODS: A total of 52 patients with refractory peripheral facial paralysis were randomized into an observation group (26 cases, 2 cases dropped out) and a control group (26 cases, 1 case dropped out). On the basis of conventional acupuncture (Yintang [GV 24+] and Yangbai [GB 14], Dicang [ST 4] at affected side, etc.), acupuncture at the infusion points of "four seas", i.e. Baihui (GV 20), Dazhui (GV 14) and bilateral Shangjuxu (ST 37), Xiajuxu (ST 39), Zusanli (ST 36), was delivered in the observation group. On the basis of conventional acupuncture, shallow acupuncture was applied at corresponding non-meridian and non-acupoint points of the infusion points of "four seas" in the control group. The needles were maintained for 30 min, the treatment was given once every other day, 3 times a week for 4 weeks in the two groups. Before and after treatment, the House-Brackmann (H-B) facial nerve grading and the dynamic view score of the facial nerve function scoring system were observed, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the H-B facial nerve grading was improved compared with that before treatment in the two groups (P<0.05), and the grading in the observation group was superior to that in the control group (P<0.05); the dynamic view scores of the facial nerve function scoring system were increased compared with those before treatment in the two groups (P<0.05), and the score in the observation group was higher than that in the control group (P<0.05). The total effective rate was 91.7% (22/24) in the observation group, and that in the control group was 84.0% (21/25), there was no significant difference in the total effective rate between the two groups (P>0.05). The cure rate was 62.5% (15/24) in the observation group, which was higher than 20.0% (5/25) in the control group (P<0.05). CONCLUSION: On the basis of conventional acupuncture, acupuncture at infusion points of "four seas" can effectively treat refractory peripheral facial paralysis, improve the facial nerve function and increase the cure rate.

Refractory pruritus caused by sintilimab and its clinical management: A case report.

Several immune related adverse events (irAEs) were reported with the wide application of immune checkpoint inhibitors (ICIs) in tumors. ICI-related skin reactions are the most common, which are manifested as maculopapules, rash, pruritus, vitiligo, psoriasis, and lichenoid rash.Among them, the incidence of pruritus is second only to maculopapule/rash, but both often co-exist. The severity of pruritus is mostly mild to moderate and can be relieved after symptomatic treatment with antihistamines. Symptoms are slightly relieved after conventional treatment in patients with severe pruritus, but it easily recurs and eventually develops into refractory pruritus.The patient's quality of life may be affected and may also be life-threatening. We report a case of a patient with postoperative recurrence of gallbladder neuroendocrine carcinoma,who developed refractory pruritus after sintilimab use, which was relieved after naloxone infusion after unsuccessful conventional drug therapy. By analyzing the treatment plan of this typical case of immune-related refractory pruritus after using sintilimab, this report discusses how clinical pharmacists can provide individualized treatment of patients by using their expertise and clinicians' cooperation and complementation in treating clinically difficult cases. This case report may be used as a reference in treating patients with refractory pruritus after the clinical use of sintilimab.

Evaluation of transurethral GreenLight laser-selective vaporization for refractory overactive bladder in women.

Background: Refractory overactive bladder (OAB) in women is a common yet challenging condition for which traditional treatments have been unsatisfactory. This study aimed to evaluate the efficacy and safety of transurethral bladder mucosal GreenLight laser-selective vaporization for treating refractory OAB in women. Methods: The female patients with refractory OAB who were admitted to the Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University between May 2022 and July 2023 were examined retrospectively in this study. Transurethral bladder mucosal GreenLight laser-selective vaporization was used to treat the patients, and the perioperative and postoperative parameters were reviewed and compared. Bladder mucosa was examined by immunohistochemical staining to explore the expressions of TRPV1, P2X3, tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) before and after treatments. Results: Surgeries were performed successfully for all 32 patients in 57.38±11.22 minutes with minimal intraoperative bleeding. Twelve weeks post-surgery, there was a significant decrease (P<0.05) in the patients' Overactive Bladder Symptom Score (OABSS), 3-day bladder diary (daytime frequency, nocturia, urgency, and urgency incontinence), and Overactive Bladder questionnaire Short Form (OAB-qSF) score. After treatments, both first desire to void (FDV) and maximum bladder pressure capacity (MCBC) increased significantly (P<0.05). The immunohistochemical analysis revealed that the GreenLight laser significantly reduced the expressions of TRPV1, P2X3, TNF-α, and IL-6 in the bladder mucosa (P<0.05). No severe complications were observed after interventions. Conclusions: For female patients with refractory OAB who have shown poor response to conventional treatment approaches, transurethral bladder mucosal GreenLight laser-selective vaporization may represent a promising alternative treatment option.

Evaluating pirtobrutinib for the treatment of relapsed or refractory mantle cell lymphoma.

INTRODUCTION: Mantle cell lymphoma (MCL) is an uncommon non-Hodgkin lymphoma that is generally considered incurable. Covalent BTK inhibitors (cBTKi) are the cornerstone of treatment for relapsed or refractory (R/R) MCL, but treatment options are limited and prognosis is poor after cBTKi failure. Pirtobrutinib is a non-covalent BTK inhibitor that has demonstrated excellent efficacy and safety and represents an important new treatment in the evolving treatment landscape of R/R MCL. AREAS COVERED: This review will provide an overview of the therapeutic landscape of R/R MCL, characteristics of pirtobrutinib, and efficacy and safety data of pirtobrutinib in R/R MCL from pivotal clinical trials. PubMed and major hematology conference proceedings were searched to identify relevant studies involving pirtobrutinib. EXPERT OPINION: For patients with R/R MCL that has progressed after treatment with cBTKi, pirtobrutinib is an important and efficacious treatment that confers favorable outcomes. In the post-cBTKi setting, when chimeric antigen receptor (CAR) T-cell therapy is not available or feasible, pirtobrutinib is the preferred treatment for R/R MCL. How to sequence or combine pirtobrutinib with CAR T-cell therapy and other available or emerging therapies requires further investigation. Future studies should also explore the role of pirtobrutinib in earlier lines of therapy for MCL.

Unraveling the complexity - Insights and interventions of refractory vernal keratoconjunctivitis.

Vernal keratoconjunctivitis (VKC) is a chronic severe ocular allergic inflammation mostly observed in children and young adults. The ocular manifestations are the expression of multifactorial immune mechanisms that generally have a good prognosis, however long-term inflammation may remarkably reduce the visual function due to complications and poor therapeutic responses. Lack of responsiveness to a drug or treatment is relatively common in VKC and it is not only due to corneal involvement, which is considered the main sign of severity. The concept of refractory may be relative to multiple factors including the clinical condition, systemic co-morbidities, previous or concomitant drugs or regiments, compliance, patient's psychological condition or expectations, type of exposome and environmental conditions, doctor's experience and expectations, or timing of clinical evaluation. In this narrative review, the authors propose a definition of refractory VKC based on revised literature and clinical experience and consider potential new treatments for refractory patients and surgical management in case of complications.

The long-term outcomes in drug-resistant epilepsy patients who underwent subtotal hemispherotomy: A single-center retrospective cohort study.

OBJECTIVE: To evaluate the long-term outcomes of subtotal hemispherotomy (SH) in treating drug-resistant epilepsy caused by unilateral hemispheric lesions and try to give the prognostic factors for these outcomes. METHODS: We retrospectively reviewed the clinical data of 19 patients who underwent SH in Sanbo Brain Hospital, Capital Medical University, Beijing, China, from May 2008 to April 2021. All clinical data and factors related to surgical and functional outcomes, including motor, neuropsychiatric, and language function, were collected and analyzed. RESULTS: The surgical outcomes showed 13 (68 %) patients were seizure-free at the last follow-up (2-14 years, mean: 5.6±2.9). No changes were found in motor outcomes in 12 (63 %) patients; seven (37 %) patients had new permanent motor deficits (NPMD). Improvement in the full-scale intelligence quotient (FIQ) (p = 0.009) was observed. Univariate analysis found that patients who did not achieve seizure freedom had a significantly older age at surgery (p = 0.017) and acute post-operative seizures (APOS) (p = 0.046). Kaplan-Meier analysis also identified significant differences in seizure outcomes between the children and adult subgroups (p = 0.0017). Multivariate Cox analysis showed that older age at surgery (HR=1.055, p = 0.034) was associated with shorter time-to-seizure-recurrence. Resection of the central operculum and insula (OR= 80.433, p =0.031) and higher monthly seizure frequency (OR= 1.073, p = 0.040) were also poor prognostic factors for motor function outcomes. CONCLUSION: SH is an effective treatment procedure in treating patients with drug-resistant epilepsy caused by hemispheric lesions with satisfied seizure outcomes, limited impairment of motor function, and preserving neuropsychiatric outcomes.

Real-world Treatment Sequencing and Outcomes With Cabozantinib After First-line Immune Checkpoint Inhibitor-based Combination Therapy For Patients With Advanced Renal Cell Carcinoma: CARINA Study Results.

INTRODUCTION: Real-world data are limited on treatment sequencing and outcomes after first-line (1L) immune checkpoint inhibitor (CPI)-based combination treatment of advanced renal cell carcinoma (aRCC). PATIENTS AND METHODS: In this real-world, UK-based, retrospective study (CARINA; NCT04957160), data were obtained from hospital and electronic prescribing records. Patients were aged ≥ 18 years at aRCC diagnosis and had received 1L CPI-CPI or tyrosine kinase inhibitor (TKI)-CPI combination therapy before second-line (2L) therapy including cabozantinib. We describe treatment outcomes including 1L and 2L durations of treatment (DoT) and overall survival (OS). RESULTS: Data from April 2015 to June 2022 were collected on 281 patients from nine UK centres. Median 1L DoT was 2.3 months for CPI-CPI therapy (n = 171) and 5.0 months for TKI-CPI therapy (n = 58). After 1L CPI-CPI or TKI-CPI therapy, median 2L DoT was 5.8 versus 4.2 months, respectively, for cabozantinib (n = 163), and 3.8 versus 2.4 months for other therapies (n = 118); median 2L OS was 15.2 and 15.3 months, respectively, for cabozantinib, and 14.6 and 24.2 months for other therapies. CONCLUSION: DoT for 2L treatment was numerically better for cabozantinib than for other therapies, and after 1L CPI-CPI therapy than after 1L TKI-CPI therapy. Median OS was similar for 2L cabozantinib and other 2L therapies, and median OS for 2L cabozantinib was similar after both 1L therapy types. These results demonstrate the antitumour effect of 2L therapies, including cabozantinib, after 1L CPI-based combination treatment, regardless of whether 1L CPI-CPI or TKI-CPI therapy is used.

Management of Severe Pain in a Case of Sensory Guillain-Barre Syndrome.

Guillain-Barre syndrome (GBS) is an acute post-infectious polyradiculoneuropathy characterized by autoantibodies targeting host antigens, resulting in nerve fiber demyelination and axonal degeneration. While symmetric ascending weakness is typical, neuropathic pain is a common yet variable manifestation. We present a case of a 52-year-old man with progressive bilateral leg weakness and severe neuropathic pain following a flu-like illness. Despite conventional analgesics, his pain persisted, necessitating a unique pain management approach. The patient's examination revealed hyporeflexia and sensory deficits consistent with GBS. Diagnostic workup, including lumbar puncture, showed albuminocytologic dissociation. Plasma exchange therapy was initiated, but severe nocturnal neuropathic pain persisted, exacerbating during treatment. Conventional pain medications were ineffective, prompting a multimodal approach. Combining hydromorphone and lorazepam provided significant pain relief, enabling completion of plasmapheresis sessions. This regimen, supplemented with gabapentin, proved effective in managing both GBS-associated and treatment-induced pain. This case underscores the debilitating nature of GBS-related pain and the importance of tailored pain management strategies. While conventional agents may fail, a multimodal approach, including opioids and adjunctive medications, can offer relief, facilitating essential treatments like plasmapheresis. Careful monitoring is imperative to mitigate risks associated with potent analgesics. Our experience contributes to the armamentarium for managing GBS-related pain, emphasizing individualized care to improve patient outcomes.

Case report: Effective treatment of rituximab-resistant minimal change disease with obinutuzumab in an adult.

Background: Minimal change disease (MCD) is a common cause of adult nephrotic syndrome. Most adults with MCD achieve complete remission (CR) after initial steroid therapy. However, approximately 30% of adults who respond to steroids experience frequent relapses, becoming steroid-dependent and potentially developing refractory MCD. Treating refractory MCD in adults poses a significant challenge. Main body: A 37-year-old woman presented to the nephrology department with a 6-year history of MCD. The diagnosis of MCD was confirmed via renal biopsy. She initially achieved CR with steroid treatment but experienced relapse during steroid tapering. Subsequent CR was achieved with a regimen of steroids and tacrolimus although multiple relapses occurred. Rituximab led to another CR, but its maintenance lasted only 6 months. The response to subsequent rituximab treatments was unsatisfactory. Ultimately, obinutuzumab was selected, resulting in the induction and maintenance of CR for 12 months. Conclusions: This case demonstrates the successful treatment of frequently relapsed, steroid-dependent, and rituximab-resistant MCD with obinutuzumab. Obinutuzumab is a promising therapeutic option for rituximab-resistant MCD.

Phase-Dependent Response to Electrical Stimulation of Cortical Networks during Recurrent Epileptiform Short Discharge Generation In Vitro.

The closed-loop control of pathological brain activity is a challenging task. In this study, we investigated the sensitivity of continuous epileptiform short discharge generation to electrical stimulation applied at different phases between the discharges using an in vitro 4-AP-based model of epilepsy in rat hippocampal slices. As a measure of stimulation effectiveness, we introduced a sensitivity function, which we then measured in experiments and analyzed with different biophysical and abstract mathematical models, namely, (i) the two-order subsystem of our previous Epileptor-2 model, describing short discharge generation governed by synaptic resource dynamics; (ii) a similar model governed by shunting conductance dynamics (Epileptor-2B); (iii) the stochastic leaky integrate-and-fire (LIF)-like model applied for the network; (iv) the LIF model with potassium M-channels (LIF+KM), belonging to Class II of excitability; and (v) the Epileptor-2B model with after-spike depolarization. A semi-analytic method was proposed for calculating the interspike interval (ISI) distribution and the sensitivity function in LIF and LIF+KM models, which provided parametric analysis. Sensitivity was found to increase with phase for all models except the last one. The Epileptor-2B model is favored over other models for subthreshold oscillations in the presence of large noise, based on the comparison of ISI statistics and sensitivity functions with experimental data. This study also emphasizes the stochastic nature of epileptiform discharge generation and the greater effectiveness of closed-loop stimulation in later phases of ISIs.

Transcranial magnetic stimulation and magnetoencephalography are feasible alternatives to invasive methods in optimizing responsive neurostimulation device placement.

Responsive neurostimulation (RNS) is a treatment option for patients with refractory epilepsy when surgical resection is not possible due to overlap of the irritative zone and eloquent cortex. Presurgical evaluations for RNS placement typically rely on invasive methods. This study investigated the potential of transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) to provide key presurgical information non-invasively. We hypothesized that these non-invasive methods may assist in optimizing RNS placement by providing useful information for seizure localization by MEG and eloquent cortex mapping by TMS. A retrospective chart review identified nine patients who underwent RNS placement (mean age = 20.4 years [SD = 5.6], two-thirds were female). Characterization of the irritative zone using MEG was successful in eight of nine patients. Non-invasive mapping of relevant eloquent cortex was attempted in all patients. TMS was successful in eight of nine patients, and MEG was successful in two of six patients. Importantly, patients mapped with non-invasive modalities experienced an average seizure reduction of 77 % at their most recent clinic visit, compared to 75 % seizure reduction in those with invasive evaluations, indicating appropriate RNS placement. These data demonstrate that TMS and MEG can provide key information for RNS and may be feasible alternatives to invasive methods for assisting in decision making regarding RNS placement. Non-invasive methods for determining RNS placement have a high rate of success when data from multiple non-invasive modalities converge and can inform more accurate placement of intracranial electrodes prior to RNS placement or mitigate their need.

IT-DEX and B cell depletion in a child with anti-GAD 65 autoimmune encephalitis presenting as NORSE: A case report.

New-onset refractory status epilepticus (NORSE) is a devastating clinical condition that often leads to severe disability. Intrathecal dexamethasone (IT-DEX) has been reported to improve refractory status epilepticus. We present an 11-year-old female with anti-GAD 65 encephalitis presenting as NORSE who had minimal response to standard anti-seizure medications and first-line immunotherapies. The patient received 6 doses of IT-DEX in conjunction with rituximab which correlated with subsequent decreased neuroinflammation, reduced seizure burden and aided in weaning anesthetic infusions. Our case with literature review suggests IT-DEX may be utilized as an early intervention in those with refractory status epilepticus from various etiologies.

Efficacy of Gastric Electrical Stimulation in Alleviating Symptoms of Refractory Post-Surgical Gastroparesis: A Retrospective Analysis from Two Centers.

BACKGROUND: Post-surgical gastroparesis, resulting from surgical interventions on the stomach or vagal nerve injury, poses significant clinical challenges with patients presenting symptoms like nausea, vomiting, and abdominal pain. While gastric electrical stimulation (GES) offers potential relief, its efficacy in refractory post-surgical gastroparesis requires further examination. OBJECTIVE: This study evaluated the clinical response to GES in patients with refractory post-surgical gastroparesis. METHODS: A retrospective study was conducted across two study sites, involving 185 patients with drug-refractory post-surgical gastroparesis who underwent both temporary and permanent GES placements. Patients were categorized based on their surgical history: Bariatric surgery, Nissen Fundoplication, and others. The impact of GES was evaluated using FDA-compliant Patient Reported Outcomes scores and other relevant clinical metrics at baseline, after temporary GES placement, and 6 months after permanent GES placement. All three groups were also analyzed by the symptom improvement group vs the non-improved group at baseline and 6 months after GES placement. RESULTS: Post-GES implantation, all patient groups significantly improved upper gastrointestinal symptoms. The bariatric surgery group and Nissen fundoplication group specifically identified anorexia as the most severe symptom post-GES after temporary GES placement among three groups (2.5 [0.4, 3.5] and 1.5 [0.0, 2.5], respectively. Nissen fundoplication patients had the highest score of anorexia among the three groups six months post-GES (3.0 [2.0, 3.5], p=0.018). Despite these improvements, GES did not enhance gastric emptying test results. Symptomatic improvements were notably significant in patients who initially reported higher symptom severity than those who did not. CONCLUSION: GES shows promise in alleviating symptoms of refractory post-surgical gastroparesis, particularly in those with severe initial symptoms. However, its impact on gastric emptying remains inconclusive. Further research is needed to establish GES as a standard treatment for post-surgical gastroparesis.

Factors Affecting Disease Stability After Intravitreal Brolucizumab Injection for Refractory Neovascular Age-Related Macular Degeneration.

INTRODUCTION: The purpose of this study is to identify the factors affecting neovascular age-related macular degeneration (nAMD) disease stability after brolucizumab treatment. METHODS: We retrospectively analyzed the medical records of 31 patients (31 eyes) with recalcitrant nAMD who were switched to brolucizumab after conventional anti-vascular endothelial growth factor (VEGF) treatment. We divided patients into two groups by treatment extension (TE) period: group 1 with TE < 12 weeks (N = 16) and group 2 with TE ≥ 12 weeks (N = 15). We compared outcomes between the groups at 2, 4, 8, and 12 weeks, including morphological characteristics of choroidal neovascularization (CNV). Logistic regression analysis identified factors associated with TE ≥ 12 weeks. RESULTS: Group 2 had a significantly greater proportion of patients with dry macula (subretinal and intraretinal fluids absent) than group 1 (60 vs. 12.5%) at 2 weeks (P < 0.05). Best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (SFCT) did not differ significantly between groups at all timepoints. Central subfield retinal thickness (CST) was significantly lower in group 2 at 2 (237.1 vs. 280.8 µm; P < 0.05), 4 (224.0 vs. 262.9 µm; P < 0.05), and 8 weeks (216.8 vs. 331.1 µm; P < 0.05). Group 2 had less vessel area (0.63 vs. 1.27 mm2; P < 0.05) and total vessel length (0.22 vs. 0.42 mm; P < 0.05). Choriocapillaris flow deficit (CCFd) was significantly lower in group 2 (42.7 vs. 48.2%; P < 0.05). Dry macula at 2 weeks (odds ratio [OR] = 8.3; P < 0.05) and a lower CCFd (OR = 0.73; P < 0.05) were associated with TE ≥ 12 weeks. CONCLUSIONS: Early fluid-free status after switching to brolucizumab and choriocapillary function around CNV were prognostic factors for disease stability in nAMD refractory to anti-VEGF treatment.

Rituximab therapy for adult refractory systemic lupus erythematosus with neurological and/or psychiatric presentations: a PRISMA-compliant meta-analysis.

BACKGROUND: Rituximab (RTX) is used off-label for refractory cases of Systemic lupus erythematosus (SLE) with extrarenal activity, including neurological and/or psychiatric (N/P) presentations. However, evidence from randomized controlled trials is limited. OBJECTIVE: This study aimed to conduct a pooled analysis of the effectiveness and safety of RTX therapy for adult refractory SLE with N/P manifestations. METHODS: Electronic searches in databases and statistical analysis were conducted in this study. RESULTS: Electronic searches in PubMed, Epistemonikos, and ICTRP in May 2023 identified 20 studies (25 reports). A total of 59 patients (53 females; 90%) were included, with a mean age of 33.5±10.6 years and a median disease duration of 3.5 years (range, 0.08 to 25.0) who were followed up post-RTX therapy for a median time of 12 months (range, 3.0 to 46.2). The rate of clinical response (partial or major) was 90% (95% CI, 83 to 96) (n = 57 patients). A third of responders relapsed after a median time of 9.5 months (range, 3.0 to 33.0). Pooled pre-RTX/post-RTX scores for Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (n = 13) were 19±15/7±5 and for neurological British Isles Lupus Assessment Group (BILAG) (n = 29) were A/D (13), A/C (5), B/D (7), B/C (2), and A/A (2). Patients without mood disorder had a higher chance of clinical response {relative risk (RR) 1.4 (1.03 to 1.48)}. Patients who benefited the most from RTX therapy were those with psychosis (a higher chance of major clinical response; RR 1.9 (1.02 to 2.34)), without acute confusional state (a lower chance of relapse; RR 0.08 (0.006 to 0.791)), and with disease duration <3 years (a lower chance of relapse; RR 0.18 (0.014 to 0.992)). Infection rate during treatment was 33% (7/21). CONCLUSIONS: RTX therapy had good effectiveness. The pooled evidence for safety outcomes was limited and of low certainty.

Defibrillation strategies for patients with refractory ventricular fibrillation: A systematic review and meta-analysis.

AIM: The aim of this study was to summarize the existing evidence about the effectiveness of double defibrillation (DD) in comparison to standard defibrillation for patients with refractory ventricular fibrillation (RVF). DD encompasses double "sequential" external defibrillation (DSeq-D) and double "simultaneous" defibrillation (DSim-D), with the study also shedding light on the respective effects of DSeq-D and DSim-D. METHODS: Investigators systematically searched PubMed, EMBASE and Cochrane Central databases for randomized controlled trials (RCTs) and cohort studies from their inception until June 06, 2024. The rate of survival to hospital discharge was the primary outcome, while the incidence of return of spontaneous circulation (ROSC), termination of ventricular fibrillation (VF), survival to hospital admission and good neurologic outcome were secondary outcomes. Relative ratios (RR) and 95% confidence intervals (CIs) were calculated for each outcome. Heterogeneity was assessed using I square value. RESULTS: A total of 6 trials, comprising 1360 patients, were included. One was an RCT, and five were observational cohort studies. The RCT showed that, compared to standard defibrillation, DSeq-D was associated with higher incidences of survival to hospital discharge, termination of VF, ROSC and good neurologic outcome. However, the pooled results of cohort studies found no benefit of DD over standard defibrillation in survival to hospital discharge (RR, 0.91; 95% CI, 0.46-1.78), nor in secondary outcomes. Furthermore, subgroup analysis suggested DSim-D was linked with lower ROSC rate compared to standard defibrillation (RR, 0.65; 95% CI, 0.49-0.86), while there was no significance between DSeq-D and standard defibrillation (RR, 1.00; 95% CI, 0.70-1.42). CONCLUSIONS: The benefit of DSeq-D in survival to hospital discharge for RVF patients was found in the RCT, but not in cohort studies. Additionally, DSim-D should be applied with greater caution for RVF patients. Further validation is needed through larger-scale and higher-quality trials. TRIAL REGISTRY: INPLASY; Registration number: INPLASY202340015; URL: https://inplasy.com/.

Outcome of gastric electrical stimulator with and without pyloromyotomy for refractory gastroparesis.

BACKGROUND: Surgical treatments of refractory gastroparesis include pyloromyotomy and gastric electrical stimulator (GES). It is unclear if patients may benefit from a combined approach with concomitant GES and pyloromyotomy. METHODS: Retrospective cohort analysis of all patients with refractory gastroparesis treated with GES implantation with and without concomitant pyloromyotomy at Cleveland Clinic Florida from January 2003 to January 2023. Primary endpoint was efficacy (clinical response duration and success rate) and secondary endpoints included safety (postoperative morbidity) and length of stay. Success rate was defined as the absence of one of the following reinterventions during follow-up: Roux-en-Y gastric bypass (RYGB), pyloromyotomy, GES removal. RESULTS: During a period of 20 years, 134 patients were treated with GES implantation. Three patients with history of previous surgical pyloromyotomy or RYGB were excluded from the analysis. Median follow-up was 31 months (IQR 10, 72). Forty patients (30.5%) had GES with pyloromyotomy, whereas 91 (69.5%) did not have pyloromyotomy. Most of the patients had idiopathic (n = 68, 51.9%) or diabetic (n = 58, 43.3%) gastroparesis. Except for preoperative use of opioids (47.5 vs 14.3%; p < 0.001), patient's characteristics were similar in both groups. There were no significant differences between the two groups in terms of overall postoperative complications (17.5% vs 14.3%; p = 0.610), major postoperative complications (0% vs 2.2%; p = 1), and length of stay (2(IQR 1, 2) vs 2(IQR 1, 3) days; p = 0.068). At 5 years, success rate was higher in patients with than without pyloromyotomy however not statistically significant (82% versus 62%, p = 0.066). Especially patients with diabetic gastroparesis seemed to benefit from pyloromyotomy during GES (100% versus 67%, p = 0.053). In an adjusted Cox regression, GES implantation without pyloromyotomy was associated with a 2.66 times higher risk of treatment failure compared to GES implantation with pyloromyotomy (HR 2.66, 95% CI 1.03-6.94, p = 0.044). CONCLUSION: Pyloromyotomy during GES implantation for gastroparesis seems to be associated with a longer clinical response with similar postoperative morbidity and length of hospital stay than GES without pyloromyotomy. Patient with diabetic gastroparesis might benefit from a combination of GES implantation and pyloromyotomy.

Plain language summary of the CARTITUDE-4 study of ciltacabtagene autoleucel for the treatment of people with relapsed or refractory multiple myeloma.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a phase 3 clinical trial called CARTITUDE-4. This trial compared the anti-cancer therapy ciltacabtagene autoleucel (or cilta-cel) with standard therapies in people who have multiple myeloma, a cancer that affects specific kinds of blood cells called plasma cells. The people in the study had been treated with 1 to 3 previous treatments for multiple myeloma, including a common anti-myeloma treatment called lenalidomide, but their multiple myeloma did not get better. HOW WAS THE STUDY IN THIS SUMMARY CONDUCTED?: About half of the 419 participants in this study received cilta-cel, while the other half received standard therapies, or therapies that are commonly used to treat multiple myeloma. Participants who received cilta-cel had a type of immune cell called T cells collected from their blood and genetically modified to recognize a specific protein found on myeloma cells. These modified T cells, which comprise cilta-cel, were then infused back into the bloodstream. WHAT WERE THE RESULTS OF THE STUDY?: After approximately 1 year in the study, more participants were alive without their cancer getting worse in the cilta-cel group (76%) than in the standard therapies group (49%). The most common side effects in both groups were infections and low blood cell counts. Cytokine release syndrome (a potentially serious side effect caused by overactivation of the immune system) was common but mostly mild. Neurotoxicities (including immune effector cell-associated neurotoxicity syndrome, which can cause symptoms such as headaches, changes in consciousness, and difficulty with memory, attention, speaking, or understanding others) were less common and were reported in 20.5% of participants treated with cilta-cel. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: In CARTITUDE-4, more participants treated with cilta-cel showed improvements and were alive with control of their disease 12 months after receiving cilta-cel compared with participants who received standard therapies.Clinical Trial Registration: NCT04181827 (CARTITUDE-4) (ClinicalTrials.gov).

Successful spinal cord stimulation using fast-acting sub-perception therapy for postoperative neuropathic pain of syringomyelia with Chiari malformation type 1: a case report and literature review.

BACKGROUND: Central neuropathic pain after foramen magnum decompression (FMD) for Chiari malformation type 1 (CM-1) with syringomyelia can be residual and refractory. Here we present a case of refractory central neuropathic pain after FMD in a CM-1 patient with syringomyelia who achieved improvements in pain following spinal cord stimulation (SCS) using fast-acting sub-perception therapy (FAST™). CASE PRESENTATION: A 76-year-old woman presented with a history of several years of bilateral upper extremity and chest-back pain. CM-1 and syringomyelia were diagnosed. The pain proved drug resistant, so FMD was performed for pain relief. After FMD, magnetic resonance imaging showed shrinkage of the syrinx. Pain was relieved, but bilateral finger, upper arm and thoracic back pain flared-up 10 months later. Due to pharmacotherapy resistance, SCS was planned for the purpose of improving pain. A percutaneous trial of SCS showed no improvement of pain with conventional SCS alone or in combination with Contour™, but the combination of FAST™ and Contour™ did improve pain. Three years after FMD, percutaneous leads and an implantable pulse generator were implanted. The program was set to FAST™ and Contour™. After implantation, pain as assessed using the McGill Pain Questionnaire and visual analog scale was relieved even after reducing dosages of analgesic. No adverse events were encountered. CONCLUSION: Percutaneously implanted SCS using FAST™ may be effective for refractory pain after FMD for CM-1 with syringomyelia.