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INTRODUCTION: We aimed at evaluating the safety and efficacy of self-expandable metallic stent (SEMS) insertion for managing patients with benign gastric outlet obstruction (GOO). METHODS: This prospective interventional study included 23 patients. All consecutive treatment-naïve symptomatic patients with benign GOO were recruited. Fully covered SEMS were deployed across the stricture under fluoroscopic and endoscopic guidance. Technical success, clinical success and sustained treatment response (STR) were assessed. Technical success was defined as the successful deployment of SEMS at the desired anatomic location. Clinical success was defined as the resolution of symptoms and an increase in Gastric Outlet Obstruction Scoring System (GOOSS) of at least 1 point from the baseline score on Day 7. STR was assessed at four and eight weeks post stent removal in patients who had a response at week four. Factors associated with stent migration and non-response at week four were also assessed. RESULTS: The median age of the study population was 30 years (range 19-65 years). Males constituted 65.22%. Most patients presented with vomiting (100%) and abdominal pain (95.65%). Peptic stricture was most common etiology for GOO (60.9%) followed by tubercular (26.1%) and corrosive (13%). Most common site of obstruction was junction of first and second part of duodenum (69.57%) followed by pyloric (30.43%). Median length of stricture was 2 cm (range 1.5-4). Technical success was achieved in all 23 patients (100%). Clinical success was achieved in 21 patients (91.3%). Response at Day 28 was seen in 20 patients (86.95%). Eighteen of 20 (90%) patients who had a response at week four had STR at week four and week eight after stent removal. Stent migration occurred in five (21.7%) patients. On univariate analysis, stricture length, calibre and stent length were found to predict migration. CONCLUSIONS: Fully covered SEMS was an effective and safe management modality in patients with benign GOO. Stent migration remains a troublesome disadvantage.

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Respiratory syncytial virus (RSV) causes respiratory disease and complications in infants, the elderly and the immunocompromised. While three vaccines and two prophylactic monoclonal antibodies are now available, only one antiviral, ribavirin, is currently approved for treatment. This review aims to summarize the current state of treatments directly targeting RSV. Two major viral processes are attractive for RSV-specific antiviral drug discovery and development as they play essential roles in the viral cycle: the entry/fusion process carried out by the fusion protein and the replication/transcription process carried out by the polymerase complex constituted of the L, P, N and M2-1 proteins. For each viral target resistance mutations to small molecules of different chemotypes seem to delineate definite binding pockets in the fusion proteins and in the large proteins. Elucidating the mechanism of action of these inhibitors thus helps to understand how the fusion and polymerase complexes execute their functions. While many inhibitors have been studied, few are currently in clinical development for RSV treatment: one is in phase III, three in phase II and two in phase I. Progression was halted for many others because of strategic decisions, low enrollment, safety, but also lack of efficacy. Lessons can be learnt from the halted programs to increase the success rate of the treatments currently in development.

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Context: The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically. Objective: To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population. Design: Retrospective cohort study. Methods: We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion. Results: UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery. Conclusions: UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.

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Background Antimicrobial resistance by bacteria poses a substantial threat to morbidity and mortality worldwide, and treatment of resistant infections is a challenge for the treating clinician. Levonadifloxacin is a novel broad-spectrum agent belonging to the benzoquinolizine subclass of quinolone, which can be used by both oral and intravenous administration for the treatment of infections caused by gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA). Patients and methods This prescription event monitoring study captured data from 1266 patients receiving levonadifloxacin (oral and/or IV) in a real-world setting to assess the safety and efficacy in the treatment of various bacterial infections. The duration of the study was 18 months. Study outcomes were clinical success and microbial success at the end of therapy. Global assessments were done for safety and efficacy at the end of therapy using a 5-point Likert scale (excellent, very good, good, satisfactory, and poor). Results The mean (median) duration of therapy was 7.2 (7.0) days, with a median time to clinical improvement of four days. Oral therapy was administered to 224 patients; 940 received IV, and 102 received IV followed by oral therapy. Patients were prescribed levonadifloxacin for gram-positive infections, skin and soft tissue infections, diabetic foot infections, septicemia, catheter-related blood-stream infections, bone and joint infections, febrile neutropenia, and respiratory infections, including COVID-19 pneumonia. The clinical cure on the eighth day was 95.7%, whereas the microbial success on the eighth day was 93.3% (n=60). For different types of infections, the clinical success rates ranged from 85.2% to 100%. There were only 30 treatment-emergent adverse events reported in 29 patients. Overall, about 95.6% of patients rated the efficacy as good to excellent, whereas only 3.8% of patients rated it satisfactory; for safety, 95.7% of patients rated it as good to excellent, with only 3.9% of patients rated it as satisfactory. Conclusions The excellent safety and efficacy profile of levonadifloxacin, when administered as an oral or intravenous therapy, makes it a desirable treatment modality for the management of various bacterial infections, including those caused by resistant pathogens such as MRSA and quinolone-resistant Staphylococcus aureus (QRSA). Features of levonadifloxacin, such as availability in both IV and oral form, minimal drug-drug interactions, lack of the need to adjust dosages in renal and hepatically impaired patients along with a broad spectrum of coverage, make it a suitable agent that meets several unmet clinical needs of physicians.

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Peroral endoscopic myotomy (POEM) has revolutionized the therapeutic strategy for achalasia with promising results. We conducted this meta-analysis to compare clinical outcomes between Eastern and Western countries. A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science and Cochrane Library databases to query for studies that assessed the efficacy of POEM for achalasia. All articles published from inception to December 31, 2021 were included. The primary outcome was the pooled clinical success rate. The secondary outcomes included the pooled technical success rate, incidence of adverse events, procedure time and hospital stay. Eighteen Eastern studies involving 5962 patients and 11 Western studies involving 1651 patients were included. The pooled clinical success rate and technical success rate for POEM was equal in the Eastern studies compared to Western studies. The pooled incidence of procedure adverse events for POEM was a little lower in the Eastern studies compared to Western studies (6.6% vs. 8.7%). Similarly, the incidence of reflux-related adverse events was lower in Eastern studies than that in Western studies. The pooled procedure time of POEM was shorter in Eastern studies compared to Western studies (61 minutes vs. 80 minutes), while the length of hospital stay was longer in Eastern studies compared to Western studies (5.8 days vs. 2.4 days). Overall, Eastern countries have the similar POEM outcomes compared to Western countries. However, Eastern countries still need to do more to reduce the length of hospital stay.

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INTRODUCTION: Long-term clinical success of non-splinted, posterior, and short implants still is unclear. This prospective cohort study reports the 10-year follow-up of 6-mm implants supporting single crowns in the posterior region, and patient-reported outcomes. METHODS: Baseline sample comprised 20 patients treated with 46 screw-retained crowns supported by 6-mm implants with moderately rough implant surface. Participants were recalled for a 10-year clinical follow-up to assess survival rates, biologic and mechanic conditions, quality of life (OHIP-14), and treatment satisfaction. Data were collected with clinical-radiographic exams and analyzed using descriptive and inferential statistics. RESULTS: Fourteen patients with 35 implant-crown units were examined after 127.6 ± 11.8 months. For the entire cohort period, 7/46 implants were lost (survival estimate: 77.7% at 133 months), and mechanic complications occurred in 14/46 units (survival estimate: 66.4% at 116 months). In the Cox models, "maximum occlusal force" had a significant effect for implant loss (p = 0.038) and for prosthetic screw loosening (p = 0.038); "arch" and "bruxism" were not significant. Peri-implant bone loss was 0.4 ± 0.6 mm at 10 years. For peri-implant bone level, "crown-to-implant ratio" (p < 0.001) and "time" (p = 0.001) were significant. Bone levels differed from baseline to 12, 48, and 120 months. Satisfaction VAS was 94.0 ± 7.9 mm and OHIP-14 was 2.3 ± 2.2. CONCLUSION: Single screw-retained crowns supported by 6-mm implants have an acceptable long-term clinical performance, with stable peri-implant bone levels after 10 years of function.

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Endoscopic adenoidectomy with powered instruments,a challenge in resource-constraint developing countries, has been on the rise. To evaluate conventional curettage as compared to endoscopic assisted adenoidectomy in the successful management of adenoid enlargement. A randomized controlled double-blinded study among children undergoing adenoidectomywas done. Primary outcomes were assessed by pre- and postoperative evaluation with a symptoms questionnaire and fiberoptic nasal endoscopy. There were 71 children aged 3-15 years, majority having grade III adenoids. Conventional adenoidectomy was done by the surgeon who was blinded to preoperative adenoid status. Patients were randomized to two groups, 35in conventional curettage where no further on-table intervention was done. Check endoscopyof the remaining 36 patients, formingthe second group, revealed residual grade III adenoidsin 5.6%. They underwentcompletion adenoidectomyendoscopically. By the 12th postoperative week, nasal endoscopy noted that 39.3% had grade I/II and 8.8% had grade I in the conventional and endoscopic groups respectively. Thoughstatistically significant, all pre-op symptoms settled except sleep-related ones which persisted in both groups (25% versus 14.7) with no complications in either group. Relief of all symptoms other than sleep-related ones, was achieved despite residual adenoids being up to grade II in both conventional and endoscopic group. This suggests non-obstructive causes in a subset of these patients. Conventional adenoid curettage is comparable to endoscopic adenoidectomy by cold method among children aged three and above. Complete adenoidclearance for achieving 'anatomical success' appears not to be necessary for 'clinical success'.

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Background: Factors related to clinically meaningful outcomes for pediatric patients seeking care for severe obesity are not well known. Examining patient-level and program-level characteristics related to success may inform future care. Objectives: To determine factors associated with a clinically significant reduction in weight status measured by %BMIp95 after 6 months of treatment. Study Design: This is a retrospective study of youth 5-17 years of age seeking multicomponent weight management care to determine if patient characteristics, treatment recommendations, reported adherence, and additional program-affiliated class participation are associated with 6-month change in %BMIp95. Results: Among 170 children with obesity, higher reductions in %BMIp95 were seen in those with medium-high dietary adherence compared to low-none (-10.8 vs. -4.0, p = 0.002). Post hoc analysis showed higher dietary adherence among those with private insurance than public insurance (59% vs. 41%, respectively, p = 0.04). Conclusion: Children receiving multidisciplinary multicomponent weight management, who achieve clinically meaningful outcomes, are more likely to be adherent to dietary recommendations regardless of the type. Further study is needed of how best to address social determinants of health to improve dietary adherence. Clinical Trial Registration Number: NCT02121132.

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OBJECTIVES: This clinical report aims to highlight the factors affecting the clinical success of alveolar ridge mini-implants used for orthodontic anchorage and provide an overview of the biomechanical versatility of this miniscrew and steps involving the proper technique of its placement. METHODS: For this clinical report, charts for 295 patients who had temporary anchorage devices (TADs) were screened. Twenty patients [15 females and 5 males: mean age = 38.15 ± 15.10 years] with 50 alveolar ridge mini-screws were assessed. A descriptive summary of the main factors affecting their clinical success and the technique employed for their placement was comprehensively discussed and illustrated, in addition to the presentation of some clinical cases illustrating their potential clinical uses. RESULTS: The survival duration (7.32 ± 9.01 months) and clinical success of the alveolar ridge mini-implants that failed (19/50) seem to be affected primarily by 2 factors: splinting; none of the splinted mini-implants failed (0/10) compared to (19/40) of the single mini-implants that failed, and the length of the used mini-implant; the average length of the mini-implants that did not fail was 9.23 mm. Additionally, it appears that these mini-implants are biomechanically robust and durable, those that did not fail had an average survival duration of 35.97 ± 19.79 months. CONCLUSION: Ridge mini-implants offer significant biomechanical versatility in patients with partially edentulous ridges needing complex pre-prosthetic orthodontic movements. The presence of splinting and the length of the used mini-implants are factors that might affect the clinical success of the alveolar ridge mini-implants.

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Despite the promising features and aggressive research, the success of nanoparticles in clinical trials is minimal. This manuscript discusses the complex biological barriers that impede the journey of nanoparticles to the target site and the approaches used to overcome them. The '6R' framework (right route, right target, right design, right patient, right combination and right technology) is proposed to improve the clinical translation of nanomedicines. Disease-driven approach contrary to the traditional formulation-driven approach is suggested. Data-driven methods can analyze the relationships between various diseases, patient pathophysiology and the physicochemical properties of different nanomedicines, aiding in the precise selection of the most appropriate treatment options. Further research is needed to evaluate and refine these approaches to develop nanomedicines for clinical success.

Plenty of work is happening in the field of nanomedicine, but only a few nanomedicines have hit the market. This could be due to many reasons. One of the major reasons is their complex biology. It is imperative to understand how the body reacts to nanomedicines. Obstacles imposed by the body and ways to overcome them are highlighted in this work. The principles of successful nanomedicine design are discussed. This includes proper selection of route, target, design, patient, combination and technology. A framework for evaluating the success of nanomedicine is also proposed. Nanomedicines should be designed using a disease-driven approach. This will help make nanomedicine more viable. Further research is required to test the validity of the proposed model.

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PURPOSE: Transarterial embolization of renal artery branches (RTE) is a minimally invasive procedure commonly performed in life-threatening renal bleeding of different etiologies. Despite the widespread use of RTE, no consensus guidelines are currently available. Our aim was to investigate clinical and technical efficacy and to identify potential predictors for clinical failure of this procedure. METHODS: All the RTE procedures performed in our Interventional Radiology unit in last 10 years were retrospectively collected and analyzed. All selected patients underwent both pre-procedural computed tomography angiography (CTA) and post-procedural CTA within 30 days. Clinical success was considered as primary endpoint. Demographic, laboratory, and diagnostic findings predictive of clinical failure of RTE were identified. RESULTS: Over a total of 51 patients enrolled, 27 (53%) were females and 33 (64.7%) had a renal bleeding of iatrogenic origin. Technical and clinical success was 100% and 80.4%, respectively. Hematoma volumes > 258.5 cm3 measured at CTA, higher pre- and post-procedural serum creatinine (Scr) levels, an increase in Scr value > 0.135 mg/dl after the procedure, a worse post-procedural estimated glomerular filtration rate (eGFR), a post-procedural reduction of eGFR < 3.350 ml/min, and a post-procedural reduction of platelet count (PLT) > 46.50 × 103/mmc showed a significantly higher rate of clinical failure. CONCLUSION: RTE is a safe and effective procedure in the management of acute renal bleeding of various origins. Hematoma volume, Scr, PLT, and eGFR values were found to be predictive factors of poor clinical outcome and should be closely monitored.

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Although CAD/CAM (computer-aided design/computer-aided manufacturing) restorations act as a favorable alternative to conventional metal-ceramic restorations for fixed dental prostheses, little is known about their intermediate and persistent clinical performance. This systematic review and meta-analysis aimed to assess the clinical performance in terms of biological, technical, and esthetic aspects and the survival and success ratios for single full crowns (SFCs) and fixed partial dentures (FPDs) fabricated by CAD/CAM and conventional techniques and according to the materials used (zirconia {ZC} and lithium disilicate {LD}). The population, intervention, control, outcome, and study design (PICOS) strategy was used to electronically search key terms in the PubMed, Cochrane Library, Embase, and Wiley Online databases for randomized control trials (RCTs) and cohort studies. The bias risks for RCTs and cohort studies were assessed using the Cochrane collaboration tool and the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using Rev5 from Cochrane. A total of 13 studies reporting on 1598 restorations in 1161 patients with a mean observation period of 3.6 years (minimum-maximum: 1-9.3 years) met the inclusion criteria. Meta-analysis of the included studies indicated that CAD/CAM manufacturing resulted in 1.17, 1.14, and 16.88 (95% CI: 0.64-2.17, 0.86-1.52, 7.59-37.56) higher biological, technical, and esthetic complications than conventional manufacturing of restorations. However, the difference was significant for esthetic complications only (p<0.00001). A significant difference was observed for all biological, technical, and aesthetic aspects between SFCs and FPDs (odds ratio {OR} = 2.61 vs. 1.78, 95% CI: 1.92-3.56 vs. 1.33-2.38; p<0.00001). The survival ratio of SFCs was 2.69 (95% CI: 1.98-3.65), significantly higher compared to the 1.76 (95% CI: 1.31-2.36) of FPDs (p<0.00001). The success ratio of FPDs at 1.18 (95% CI: 0.83-1.69) was significantly lower compared to SFCs at 2.36 (95% CI: 1.68-3.33). The clinical performance of LD with 2.42 (CI: 1.16-5.03) was significantly higher compared to ZC with 2.22 (CI: 1.78-2.77) (p<0.00001). The biological, technical, and aesthetic behaviors showed similar clinical outcomes between the CAD/CAM and conventional groups. LD could be a good alternative to zirconia, but its intermediate or persistent clinical performance needs to be evaluated. Overall, zirconia and CAD/CAM techniques must evolve further to outclass the conventional techniques used in the fabrication of SFCs and FPDs.

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BACKGROUND: With the difficulties in choosing colistin sulfate and polymyxin B sulfate (PBS) for carbapenem-resistant gram-negative bacteria (CR-GNB), we compared the efficacy and safety of these two old polymyxins in treatment of critically ill patients infected with CR-GNB infection. METHODS: One hundred four patients infected with CR-GNB in ICU were retrospectively grouped by PBS (68 patients) or colistin sulfate (36 patients). Clinical efficacy including symptoms, inflammatory parameters, defervescence, prognosis and microbial efficacy were analyzed. Hepatotoxicity, nephrotoxicity, and hematotoxicity were evaluated by TBiL, ALT, AST, creatinine, and thrombocytes. RESULTS: Demographic characteristics between colistin sulfate and PBS were not significantly different. Most of the CR-GNB were cultured in respiratory tract (91.7% vs 86.8%), and almost all were polymyxin-sensitive (98.2% vs 100%, MIC ≤ 2 µg/ml). The microbial efficacy in colistin sulfate (57.1%) was significantly higher than PBS (30.8%) (p = 0.022), however, no significant difference in clinical success was seen in both groups (33.8% vs 41.7%), as well as mortality, defervescence, imaging remission, days in the hospital, microbial reinfections, and prognosis, and almost all patients defervesce within 7 days (95.6% vs 89.5%). CONCLUSIONS: Both polymyxins can be administrated in critically ill patients infected with CR-GNB and colistin sulfate is superior to PBS in microbial clearance. These results highlight the necessity of identifying CR-GNB patients who may benefit from polymyxin and who are at higher risk of mortality.

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Tooth loss due to fracture and the failure of endodontic treatment (ET) are common situations in teeth with extensive tissue destruction. This is due to the fragility of the remaining dental structure and the difficulty in sealing cavities, which is sometimes associated with the violation of the supracrestal insertion tissue. The previous restoration of marginal ridges or cusps with composite resin (CR) restores their fracture resistance, due to the adhesive characteristics of the restorative material, while also protecting the quality of endodontic treatment through better sealing. However, the protocol adopted in teeth requiring endodontic treatment involves performing the restorative procedure only after the endodontic procedures. The objective of this study was to report a case in which restoration of marginal ridges and/or cusps was performed prior to endodontic treatment, focusing on maintaining the tooth in function without dental fracture. The restoration was performed with an inverted operative sequence before the endodontic treatment. There was a violation of the supracrestal insertion tissue, requiring crown lengthening surgery (CLS) prior to the restorative procedure. Clinical and radiographic evaluations were performed postoperatively at seven days, three, six, and nine months, and five years. Tooth function was maintained without dental fractures or restoration loss. Periradicular space healing occurred with the disappearance of the lesion. Performing the restorative procedure prior to endodontic treatment in teeth with extensive coronal destruction is an alternative technique that facilitates clinical procedures, reduces the likelihood of dental loss due to fracture, and promotes endodontic treatment success.

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BACKGROUND: The use of transcatheter adrenal ablation as an alternative treatment for primary aldosteronism (PA) patients remains a subject of debate, with outcomes varying widely across existing studies. This meta-analysis aims to evaluate the results of adrenal ablation and estimate the effectiveness and safety of this therapeutic approach. METHODS: A comprehensive search was conducted across PubMed, Embase, and Cochrane Library databases for studies published up to October 2022. Outcomes analyzed included the combined clinical success rate, biochemical success rate, and complication rate, which were assessed using a random-effects model. RESULTS: Five studies, comprising 234 PA patients, were included in the analysis. The combined clinical success rate was 74% (95% CI: 69%-79%), and the biochemical success rate was 74% (95% CI: 53%-95%). Subgroup analysis revealed that the combined clinical success rate from Unilateral PA (72%, 95% CI: 46%-98%) was similar to the rate from Unilateral + Bilateral (73%, 95% CI: 52.0%-94.0%), while the clinical success rate of the PASO subgroup (78%, 95% CI: 66.0%-89.0%) was higher than the rate of other criteria (51%, 95% CI: 40.0%-63.0%). The combined complication rates were as follows: mild fever, 23% (95% CI: 12%-33%); back pain, 84% (95% CI: 77%-91%); and pleural effusion, 9% (95% CI: 0%-18%). All complications resolved within one week following the procedure. No late complications or ablation-related deaths were reported. CONCLUSIONS: Transcatheter adrenal ablation for PA patients is safe and demonstrates a relatively high clinical success rate. Presently, this approach is suitable for PA patients who are unwilling to undergo surgery or receive long-term mineralocorticoid receptor antagonist (MRA) treatment. SYSTEMATIC REVIEW REGISTRATION: INPLASY, identifier 2022110076.

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Background With the improvement in noninvasive diagnostic imaging modalities, Endoscopic Retrograde Cholangio-Pancreatography (ERCP) has evolved into a primarily therapeutic procedure. Besides being efficacious and one of the most commonly done procedures, ERCP is also associated with a high risk of complications. However, there is a lack of studies analyzing the safety and success of ERCP in patients with liver cirrhosis. We retrospectively evaluated the outcome of ERCP in patients with cirrhosis of the liver compared to non-cirrhotic patients using the database from our institute. Methods Patients with liver cirrhosis who underwent ERCP from January 2010 to March 2020 were analyzed. This was a matched case-control study in which one cirrhotic patient undergoing ERCP was age and gender-matched randomly to one non-cirrhotic patient. We compared adverse events and the success rate of ERCP between cirrhotic patients and non-cirrhotic patients. The primary outcome of the study was analyzing the prevalence of procedure-related adverse events and their independent risk factors in patients of cirrhosis compared to the non-cirrhotic population. Results Two hundred patients were analyzed in both groups. Choledocholithiasis was the most common reason for ERCP in both groups. Mean Child-Turcotte-Pugh (CTP) score and Model for End-stage Liver Disease (MELD) score in the cirrhosis group were 9.16 ±1.78 and 19.09 ±7.06 respectively. Patients in the cirrhosis group had a significantly higher frequency of complications compared to the controls: 41 (20.5 %) versus 15 (7.5%), p < 0.01. Bleeding was the most common adverse event in both groups: 19 (9.5%) vs 6(3%). High International Normalised Ratio (INR), low platelets, and cholangitis at presentation were independently predictive of post-ERCP complications. Despite a similar technical success rate, the clinical success rate was lower in the cirrhotic than in the noncirrhotic group (83.9% versus 97.9%, p=0.006). Conclusion The prevalence of complications following ERCP was nearly three-fold higher in patients with cirrhosis than in non-cirrhotic patients. These events were related primarily to cholangitis, coagulopathy, and the advanced status of chronic liver disease.

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BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) achieves a satisfactory short-term clinical response in patients with achalasia. However, data on mid- and long-term clinical outcomes are limited. We aimed to assess the mid- and long-term efficacy and safety of POEM in achalasia patients. METHODS: Using the pre-designed search strategy, we identified relevant studies that evaluated the efficacy and safety of POEM with a minimum of 2-year follow-up in the Embase, Cochrane, and PubMed databases from inception to January 2021. Primary outcome was pooled mid- and long-term clinical success rate based on the Eckardt score. Secondary outcome was pooled long-term reflux-related adverse events. RESULTS: A total of 21 studies involving 2,698 patients were included. Overall, the pooled clinical success rates with 2-, 3-, 4-, and 5-year follow-ups were 91.3% (95% confidence interval [CI] 88.4-93.6%), 90.4% (95% CI 88.1-92.2%), 89.8% (95% CI 83.6-93.9%), and 82.2% (95% CI 76.6-86.7%), respectively. Besides, the pooled long-term clinical success rates for type I, II, and III achalasia were 86.1% (95% CI 80.9-90.1%; I2 = 0%), 87.9% (95% CI 84.2-90.8%; I2 = 48.354%), and 83.9% (95% CI 72.5-91.2%; I2 = 0%), respectively. Moreover, the pooled incidence of symptomatic reflux and reflux esophagitis was 23.9% (95% CI 18.7-29.9%) and 16.7% (95% CI 11.9-23.1%), respectively. CONCLUSIONS: POEM is associated with a long-term clinical success of 82.2% after 5 years of follow-up. Randomized control trials comparing POEM with laparoscopic Heller myotomy or pneumatic dilation with longer follow-up periods are needed to further demonstrate the long-term safety and efficacy of POEM.

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Background: Endoscopic retrograde cholangiopancreatography (ERCP) for patients with periampullary diverticulum (PAD) remains a challenge. This study aims to investigate the factors and techniques related to successful and safe ERCP in patients with PAD. Methods: We enrolled patients who underwent ERCP in a large tertiary center. The difficult cannulation rate, technical success rate, clinical success rate, and adverse events (AEs) rate were compared between patients with or without PAD. Three independent logistic regression models were established to identify factors and techniques associated with difficult cannulation, clinical success, and AEs. Results: Five thousand five hundred and ninety patients were included, of which 705 (12.6%) were diagnosed with PAD. Patients with PAD had a significantly higher difficult cannulation rate compared with patients without PAD (10.6% vs 8.0%, P < 0.0001), but the rates of technical success (clinical success (95.2% vs 95.2%, P = 0.951), and AEs (16.5% vs 14.4%, P = 0.156) were similar. Type I PAD (odds ratio [OR] = 2.114, 95% confidence interval [CI]:1.05-5.25) and ERCP indication for pancreatic diseases (OR = 1.196, 95%CI: 1.053-1.261) were independently associated with difficult cannulation. Small endoscopic sphincterotomy (EST) with balloon dilatation (OR = 1.581, 95%CI: 1.044-2.393) was independently associated with clinical success. Somatostatin injection showed no preventive effect on post-ERCP pancreatitis (OR = 1.144, 95%CI: 1.044-1.254). Moreover, the auxiliary cannulation techniques were safe for PAD patients. Conclusions: PAD did not affect ERCP outcomes. However, the choice of techniques and AE prophylactic measures should be more specific, especially for patients with type I PAD.

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INTRODUCTION: The scaffolds used in regenerative endodontic therapy (RET) provide structural support for cells so that they can adhere to the scaffolds and also are crucial for cellular proliferation and differentiation. The objective of this network meta-analysis was to compare effects of different intracanal scaffolds on success outcomes of RET. METHODS: PubMed/Medline, EMBASE, Cochrane, CINAHL, Scopus, and Web of Science databases were searched. Studies evaluating and/or comparing clinical and/or radiographic success of RET using different scaffolds with a minimum of 12 months follow-up were included. The Cochrane Collaboration risk of bias (ROB) tool and appropriate tools from Joanna Briggs Institute were used for the assessment of ROB. A network meta-analysis was performed to compare the primary outcome (clinical success) and other success outcomes (root maturation, and pulpal sensibility) using different scaffolds. RESULTS: Twenty-seven studies fulfilled the desired inclusion criteria of which 25 had a low ROB whereas 2 had a moderate ROB. Clinical success of RET using platelet-rich plasma (PRP), blood clot (BC), and platelet-rich fibrin (PRF) scaffolds ranged between 91.66%-100%, 84.61%-100%, and 77%-100% respectively. The different scaffolds did not show any statistically significant difference in clinical success (PRF vs BC [P = 1.000], PRP vs BC [P = 1.000], and PRF vs PRP [P = .999]), apical root closure (PRF vs BC [P = 1.000], PRP vs BC [P = .835], PRF vs PRP [P = .956]), and pulp sensibility (PRF vs BC [P = .980], PRP versus BC [P = .520], and PRF vs PRP [P = .990]). CONCLUSION: The intracanal scaffolds used during RET did not result in significant differences in regard to clinical success, root maturation, and pulpal sensibility.

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INTRODUCTION: Neuromodulation for pain has been successfully applied for decades, in that the goals and expectations that patients aim to achieve are clearly described. Nevertheless, the point of view of health care providers is less clear. Therefore, this study aimed to explore the goals, expectations, and definition of success for neuromodulation for pain according to health care providers. MATERIALS AND METHODS: An online survey was developed and spread at the 2nd Joint Congress of the International Neuromodulation Society (INS) European Chapters in September 2021 in Paris. Respondents were asked 1) to select the goals to treat patients with neuromodulation for pain, 2) to indicate factors that they expect to change according to neuromodulation for pain, and 3) to provide their definition of success of neuromodulation for pain. RESULTS: We approached 101 respondents, of whom 88 health care providers at least partly completed the survey. Increasing mobility/functionality (26.7%), decreasing pain intensity (24.5%), and decreasing medication use (16.6%) were the most frequently reported goals of neuromodulation. The same top three variables were selected as factors that health care providers expected to change. For the definition of success, quality of life of patients outranked other definitions. Other highly ranked definitions, in descending order, were obtaining pain relief, increasing functionality, and increasing patient satisfaction. DISCUSSION: Goals and expectations of health care providers are not completely in line with previously explored goals of patients that are related to pain relief and improving walking abilities. Health care providers seem to put a high emphasis on the quality of life of the patient when evaluating the success of neuromodulation, which is not completely aligned with the currently used reimbursement rules that are mainly focusing on pain relief instead of incorporating health-related quality of life. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT05013840.

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