Gastric peroral endoscopic pyloromyotomy (G-POEM) in patients with refractory gastroparesis: a review.

Gastric peroral endoscopic pyloromyotomy (G-POEM or POP) is an endoscopic therapeutic modality for treatment of refractory gastroparesis. Since the first case reported in 2013, there are more than 200 papers published on G-POEM. In this narrative review, we summarize the short-term and long-term outcomes and review other important studies. The technical success rate is 100% and the short-term (within 1 year) success rate is about 50-80%. The procedure time is between 50 and 70 min while the average length of hospital stay was 2-3 days. The adverse event rate was around 10%. Few patients need further intervention. Three studies showed that at the 4-year follow-up, the response to G-POEM was durable, but there was a yearly recurrence rate of 13% or more. Redo G-POEM is feasible and can be of benefit for some patients. Most of the studies showed that long duration of illness is associated with poor outcomes. However, reliable predictors for successful outcomes are still unknown. Current literature indicates G-POEM is superior to gastric electric stimulator and surgical pyloroplasty. Endoflip has been used at G-POEM to predict the outcome, but the result is very preliminary. A recent sham study confirms the short-term efficacy of G-POEM. G-POEM is safe and about 50% of patients can be discharged to home on the same day. G-POEM allows for direct biopsy of the gastric muscle, which is the location of the pacemaker cells, the interstitial cells of Cajal; therefore, G-POEM may provide a new path for further research on the pathogenesis of gastroparesis.

Safety and feasibility of same day discharge after per oral endoscopic pyloromyotomy in refractory gastroparesis: a pilot study.

BACKGROUND: Gastroparesis is a debilitating medical condition with limited treatment options. Gastric per-oral pyloromyotomy (G-POEM) has emerged as a promising treatment option with remarkable short-term clinical success shown in multiple studies. While the post-procedure protocol is not standardized across many centers, the majority of the centers observes these patients in the hospital after the procedure for monitoring. In this single-center prospective study, we evaluated the safety and feasibility of same day discharge after the G-POEM procedure. METHODS: All the patients with refractory gastroparesis undergoing G-POEM from October 2019 to March 2020 were enrolled. A total of 25 patients were enrolled in the procedure. Based on the pre-defined criteria, patients were either discharged on the same day after the procedure or admitted to the hospital for further observation. The patient and procedure-related data were extracted from the chart review. Univariate analysis was performed (chi-squared test) on categorical variables after organizing categorical variables as numeric counts or percentages. The student t test was performed on continuous variables after reporting as mean and standard deviation. For analysis with a smaller sample size, Fisher exact and Mann-Whitney tests were used. RESULTS: A total of 25 patients were enrolled. The technical success of G-POEM was 100% and clinical success was 80% (20/25) at 1-month follow-up. Of the 25 patients, 9 patients (36%) were discharged on the same day according to the procedure from the recovery unit. Of the remaining 16 patients who were admitted to the hospital post-procedure, 10 (40%) were admitted due to procedure-related causes while other admissions were either pre-planned or due to social reasons. The average Charlson comorbidity index was lower in the same day discharge group ( P   <  0.05). The number of patients requiring double myotomy was higher in the same day discharge group ( P  < 0.05). The overall complication rate of G-POEM in the study cohort was 12% (3/25) with all complications being mild without any severe adverse events. CONCLUSION: G-POEM is a safe and effective method of treatment for refractory GP with higher clinical success in short-term follow-up. The same day discharge after G-POEM is safe and feasible in >50% of patients with close periprocedural monitoring.

An Atypical Presentation of West Nile Virus With Successful Treatment After Plasma Exchange and Intravenous Immunoglobulin.

West Nile (WN) disease is a relatively rare arboviral virus. Neuroinvasive cases of WN account for less than 1% of the total cases. The case described had difficult symptomatology and radical presentation, which included ascending paralysis. To date, there have been very few reports of West Nile cases that present with ascending paralysis. We describe the case of a 63-year-old white male who presented with a fever and proximal muscle weakness in the thighs and legs that rapidly worsened and ascended, eventually resulting in diaphragmatic paralysis. He was intubated after respiratory failure and given intravenous immunoglobulin and plasma exchange. The patient remained ventilated with persistent weakness. However, this improved after intravenous immunoglobulin and plasma exchange therapy. This case serves as a reminder to keep the diagnosis of WN on the differential, a primer on advanced treatments in the setting of aggressive atypical WN, and a lesson on similarly presenting diseases and distinguishing characteristics that may help rule out these diseases from WN.

Quantification of Interstitial Cells of Cajal in the Gastric Muscle of Patients with Gastroparesis at Per-Oral Endoscopic Pyloromyotomy: A Novel Approach for Future Research in Pathogenesis of Gastroparesis.

BACKGROUND: The role of Interstitial Cells of Cajal (ICC) in the pathogenesis of gastroparesis has been suggested by previous studies due to their involvement in the transmission of neuronal signaling to the smooth muscles of the GI tract. However, studies have been limited by the inability to obtain a gastric muscle sample, since routine endoscopy can only biopsy the mucosa. We present a new technique of muscle biopsy during per-oral endoscopic pyloromyotomy (GPOEM), a novel endoscopic procedure for treatment of gastroparesis. PATIENTS AND METHODS: All enrolled patients had diagnosed gastroparesis and had biopsies of the muscular layer at the antrum/pylorus during POEM. All GPOEM procedures took place from August 2019 to December 2019. Various demographic, disease-related, and procedure-related data were collected from chart review. ICC in the biopsy specimen was examined and quantitated. RESULTS: Through this method, we readily expose the gastric muscle of 21 patients through dissection of a gastric submucosal tunnel during GPOEM and provide reliable muscle sample for ICC quantification. Average number of ICC were higher in clinical responders (88 ICC ± 63 vs. 39 ICC ± 24, p = 0.02), defined as those who experienced significant improvement in nausea and vomiting symptoms after GPOEM. CONCLUSIONS: This study provides a reliable novel biopsy method for safely biopsy gastric muscle for quantitating the number of gastric ICC in patients with gastroparesis. The number of ICC may be related to the outcome of GPOEM therapy. However, further studies with larger number of patients are needed to confirm the results.

Measurement of autoantibodies using multiplex methodology in patients with systemic lupus erythematosus.

Autoantibodies are central to the diagnosis and assessment of systemic lupus erythematosus (SLE). A recent technique for the measurement of autoantibodies utilizes addressable laser bead immunoassay technology (BioPlex 2200) which permits the simultaneous detection of multiple autoantibodies and improved efficiency due to the shorter time to perform the assay and low volume of test samples and reagents. In the current study we have compared this technique to more traditional measures of autoantibody detection. The clinical and laboratory data and stored serum samples from the enrollment visit into a long-term lupus registry at a single academic medical center were used. Sera were examined for a panel of autoantibodies using the BioPlex ANA screen. The results were compared to the historical data on autoantibody profiles using indirect immunofluorescence (IIF) and ELISA. The association with global and organ specific SLE disease activity (nephritis) was also examined. The study consisted of 192 patients who were predominantly female (87%) and Caucasian (91%) with mean disease duration of 8.8 years. The frequency of ANA and anti-dsDNA by IIF and ELISA was 81.3% and 46.6% respectively and was higher than that found with BioPlex (75.5% and 31.8%). The latter detected a higher proportion of patients with autoantibodies to Sm (7.5% vs 16.7%), RNP (21.8% vs 24.0%), Ro (37.4% vs 41.7) and La (13.9% vs 23.4%). Overall agreement between assays varied between 71.4% and 92.5%. Additional autoantibodies identified by BioPlex were anti-chromatin antibodies which were similar in frequency to anti-dsDNA antibodies (33.9% and 31.8% respectively). There was a low frequency of anti-ribosomal P (6.8%), anti-Scl-70 (5.2%), anti-centromere B (3.7%) and anti-Jo-1 (0.5%). Several autoantibodies revealed significant associations with SLEDAI scores but in a multivariate analysis the only autoantibodies that approached statistical significance were anti-Sm (p=0.094) measured by ELISA and anti-dsDNA (p=0.082) measured by BioPlex. There was no association between any of the autoantibodies regardless of the method of detection and cumulative organ damage scores. Fifty-three patients (27.6%) had lupus nephritis of which 17 (32%) had active nephritis at the time of autoantibody determination. There was no significant association between a positive ANA (IIF) and any autoantibodies detected by ELISA with either the cumulative occurrence of lupus nephritis or active nephritis. In contrast, there was an association between BioPlex detected anti-dsDNA with the cumulative occurrence of nephritis (p=0.074) which reached statistical significance with active nephritis at the time of antibody testing (p=0.012). This was confirmed by multivariate analysis (p=0.047). These results suggest reasonable agreement between the detection of lupus autoantibodies by ELISA and BioPlex. The latter demonstrated a better correlation with lupus nephritis.

Prospective study of neuropsychiatric events in systemic lupus erythematosus.

OBJECTIVE: To prospectively examine neuropsychiatric (NP) events and their association with health related quality of life (HRQOL) over time in patients with systemic lupus erythematosus (SLE). METHODS: In an observational cohort study from a single academic center, NP events and their attribution were identified at enrollment and at annual assessments for up to 7 years. NP events were characterized using the American College of Rheumatology case definitions; other variables were global SLE disease activity and cumulative organ damage. The outcomes of NP events were recorded and self-report HRQOL was measured with the mental (MCS) and physical (PCS) component summary scores of the Medical Outcomes Study Short Form-36. RESULTS: There were 209 patients, 88% female and 92% Caucasian, with a mean (standard deviation) age of 43.7 (13.8) years. Followup was available in 175/209 (84%) patients. There were 299 NP events in 132/209 (63%) patients over a mean followup of 3.6 (2.5) years. Thirty-one percent of NP events in 54 patients were attributed to SLE. Multivariate analysis indicated lower MCS scores in patients with NP events compared to those without events (p < 0.001) regardless of attribution. The group means for PCS scores were significantly lower in patients with NP events (p < 0.001) regardless of attribution. There was no association between HRQOL and cumulative organ damage, nor between NP events and the progression of organ damage. CONCLUSION: The association of lower HRQOL with NP events over time, which is independent of progression in cumulative organ damage, emphasizes the persistent negative effect of NP events in the lives of patients with SLE.

Neuropsychiatric syndromes in patients with systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVE: The cause of neurologic (N) and psychiatric (P) syndromes in patients with systemic lupus erythematosus (SLE) is mutifactorial and includes primary immunopathogenic mechanisms, nonspecific sequelae of chronic disease, and concurrent illnesses. We compared the prevalence, diversity, and clinical significance of NP syndromes in patients with SLE and rheumatoid arthritis (RA). METHODS: Fifty-three patients with SLE were matched by age and sex to 53 patients with RA attending ambulatory clinics in a single academic medical center. All fulfilled the American College of Rheumatology (ACR) classification criteria for either SLE or RA. Cumulative NP manifestations were determined using the ACR nomenclature and case definitions for 19 NP syndromes. Depression and anxiety were measured by the Hospital Anxiety and Depression Scales (HADS) and symptoms of cognitive dysfunction were assessed by the Cognitive Symptoms Inventory (CSI). Health related quality of life (HRQOL) was evaluated by the SF-36 and fatigue by a 10 point Likert scale. RESULTS: The patients were well matched with regard to age, sex, disease duration, and years of education. There were no significant differences in self-reported HRQOL, fatigue, anxiety, depression, and cognitive symptoms between the 2 groups. The proportion of patients with cumulative NP events was higher in RA than in SLE patients (47% vs 28%; p = 0.045), and of these the occurrence of multiple NP events in individual patients was comparable in both groups (SLE 53%; RA 48%; p = 0.75). Fifty-five percent and 66% of NP events occurred prior to the diagnosis of SLE and RA, respectively. NP events common to both SLE and RA patients were headaches, mood disorders, acute confusional states, anxiety, cerebrovascular disease, and cognitive dysfunction. Seizures and demyelinating syndrome occurred only in SLE patients, but were rare. Depression scores (HADS) were significantly higher in SLE patients with a history of cumulative NP events compared to RA patients with NP events (p = 0.02). Similarly, symptoms of cognitive dysfunction (CSI) were more common in SLE patients with a history of NP manifestations (p = 0.02). However, there were no significant differences in SF-36 subscale or fatigue scores between SLE and RA patients with cumulative NP events. CONCLUSION: NP syndromes, regardless of etiology, are common in both SLE and RA patients. SLE patients with NP syndromes report more symptoms of depression and cognitive dysfunction compared to RA patients with NP syndromes, but do not report significantly poorer HRQOL. These results emphasize the presence of non-disease-specific causes of NP manifestations in SLE patients, which should be acknowledged in future studies of pathogenesis and treatment.

Neuropsychiatric events in systemic lupus erythematosus: attribution and clinical significance.

OBJECTIVE: To describe the range and attribution of neuropsychiatric (NP) disease in an unselected cohort of patients with systemic lupus erythematosus (SLE) and to examine the association with cumulative organ damage, medication use, and quality of life. METHODS: One hundred eleven patients with SLE in a single referral center were studied. NP syndromes were defined using the American College of Rheumatology (ACR) nomenclature and case definitions. Overall disease activity was measured by the SLE Disease Activity Index (SLEDAI); cumulative organ damage was determined by the ACR/SLICC damage index; and quality of life by the SF-36. RESULTS: Patients' mean age was 44.7 years, 87% were female, and 92% were Caucasian. The mean (+/- SE) disease duration was 10.1 +/- 0.7 years. A total of 74 NP events were identified in 41 of 111 (37%) patients. Thirteen of the 19 ACR NP syndromes were identified and 2 or more NP manifestations occurred in 56% of patients. Central nervous system manifestations accounted for 92% of the events compared to involvement of the peripheral nervous system in 8%. Thirty-five (47%) of these events were attributed entirely to SLE, 30 (41%) were attributed exclusively to non-SLE factors, and in the remaining 9 events (12%) both SLE and non-SLE factors were felt to be contributory. Cumulative organ damage was higher in patients with NP disease, although this was not statistically significant and they were more likely to have received prednisone or immunosuppressive drugs (p < 0.05). Patients with NP disease reported more fatigue (p < 0.05) and had significantly lower scores on 7 of 8 subscales of the SF-36 (p < 0.05). These associations were found regardless of the attribution of NP disease. In contrast, the occurrence of renal disease in the same cohort of patients was not associated with lower SF-36 scores or fatigue. CONCLUSION: In patients with SLE, NP disease has diverse manifestations and can be attributed to lupus in roughly half of the cases. The occurrence of NP disease is associated with more frequent use of corticosteroids and immunosuppressive drugs. In contrast to other serious manifestations of SLE, such as renal disease, NP disease is associated with a significant reduction in quality of life.