Analogue Therapy Research Articles

The Combination of Nucleotide Analog Therapy and Steroid Pulse Therapy for Acute HBV Infection Effectively Promotes HBV Clearance

Acute hepatitis B virus (HBV) infection occasionally progresses to acute liver failure, often with poor prognosis. The appropriate pharmacological approach is yet to be established. Although nucleotide analogs (NA) and corticosteroids are candidates for the treatment of acute HBV infection, their therapeutic effects, especially their effect on HBV clearance, remain unclear. To clarify effects on the HBV clearance of combination therapy of NA and steroid pulse therapy (SPT) for acute HBV infection, we first analyze the effectiveness of this therapy in patients with HBV infection compared with NA monotherapy (NAM). Of the 57 consecutive patients with acute hepatitis B infection from May 2007 to December 2018, we have included 25 patients for this study, whom we followed up until HBV clearance. According to the administration of NA and SPT, we divided patients into two groups (NAM group and NA + SPT group) and compared their results. Of the 25 patients, 10 received NAM, whereas 15 received NA + SPT. There were no appreciable adverse effects related to SPT. The time required for the clearance of HBsAg (76 (43–116) days vs. 26 (14–51) days, p = 0.0418) and HBV-DNA (NAM group vs. NA + SPT group: 180 (83.5–220) vs. 69 (43–136) days, p = 0.0420) was significantly shorter in the NA + SPT group than in the NAM group. The hazard ratio of NA + SPT for the clearance of HBsAg and HBV-DNA were 0.45 (0.19–1.09) and 0.35 (0.14–0.89), respectively. In conclusion, we showed that NA + SPT promoted HBV elimination. These findings support the use of the NA + SPT combination for acute HBV infection without the concern of persistent HBV infection.

Basti Therapy (medicated enema) in gynecological practice: A way forward in managing oligo-hypomenorrhoea (Artavakshaya)

Artavakshaya (oligo-hypomenorrhoea) is a condition described in Ayurvedic classics in which vitiated vata and kapha dosha causes obstruction in the artavavahasrotas (channels that carries menstrual blood or artava). The characteric features of Artavakshaya include yathochitakalaadarshana (prolonged intermenstrual period), alpata (scanty bleeding) and yonivedana (pain in vagina or pain during menses). Artavakshaya is a condition very much similar to the oligohypomenorrhoea which is characterized by cycle which are longer than 35 days and with bleeding less than 2 days. The principles of management of Artavakshaya are vatakaphashamaka (vata and kapha dosha pacifying) and agnivardhaka (stimulant, digestive and pitta analogue) therapy. Basti (medicated enema) which comes under Panchakarma (five biopurificatory measures) is considered as superior treatment in vata and vata predominant conditions. Matrabasti (low dose medicated oil enema) is a type of anuvasana basti (medicated lipid enema) which can be administered without much contraindication. Matrabasti administered with vatakaphashamaka and agnivardhaka drug can be better choice in the treatment of artavakshaya. Basti which is administered through guda maarga (rectal route) reaches the pakwashaya (large intestine) and spreads the virya (potency) of the drug to sarvasharira (whole body) through the microchannels. Basti which can act on the enteric nervous system and thereby act on the Central Nervous System can further stimulate the Hypothalamo-Pituitary-Ovarian (HPO) axis. A well co-ordinated HPO axis can normalise the menstrual cycle.

High levels of soluble programmed death-1 are associated with virological response in chronic hepatitis B patients after antiviral treatment

BackgroundSoluble programmed cell death protein-1 (sPD-1) plays an important role in chronic hepatitis B virus (HBV) infection by counteracting the inhibitory effect of programmed death ligand-1 (PD-L1) on immune cells. Here, we investigated the ability of sPD-1 to predict the virological response (VR) in chronic hepatitis B (CHB) patients undergoing Nucleos(t)ide analogue (NA) therapy. MethodsCHB patients [hepatitis B surface antigen (HBsAg) positive ≥6 months] who initiated NA therapy in March 2007 at Peking University First Hospital (China) were enrolled in this study. Eighty-nine CHB patients were followed-up every 12 weeks for 96 weeks. ResultsSerum sPD-1 levels at baseline were negatively correlated with hepatitis B surface antigen (HBsAg) and HBV DNA. Immune-active CHB patients exhibited higher serum sPD-1 levels at baseline. Patients with VR during the antiviral treatment exhibited higher sPD-1 levels and lower HBsAg levels at baseline. Receiver operating characteristic (ROC) curves were generated to determine the predictive value of sPD-1 and HBsAg for VR in patients who received first-line therapy (entecavir, ETV). The area under ROC (AUROC) values of sPD-1 and HBsAg at baseline were 0.850 (95%CI:0.729–0.971, P = 0.0005) and 0.785 (95%CI: 0.642–0.929, P = 0.005), respectively, and the optimal cut-off values were 459.46 pg/mL and 14,710 IU/mL, respectively. The combination of sPD-1 and HBsAg exhibited a higher AUROC value (0.870,95% CI: 0.748–0.983, P = 0.001) than did sPD-1 or HBsAg alone. In patients administered second-line therapy (lamivudine, LAM/adefovir divipoxil, ADV), baseline sPD-1 levels above 677.2 pg/mL were significantly associated with higher incidence of VR after 96 weeks of antiviral therapy. It is 7.956 times the level of ≤677.2 pg/mL. ConclusionsBy combining sPD-1 and HBsAg, we obtained a biomarker significantly associated with VR in CHB patients. The sPD-1 levels could be used to screen out patients with poor prognosis of antiviral therapy.

P-P22 NET Profit: Considering quality of life assessment in patients treated with SSAs for NETs

Abstract Background Somatostatin Analogue (SSA) therapy of neuroendocrine tumours (NETs) leads to pancreatic exocrine insufficiency (PEI). PEI symptoms include diarrhoea, abdominal discomfort, bloating, and steatorrhea, which negatively impact quality of life (QoL). NETs (and the sequelae of carcinoid syndrome) however, have similar symptomatology to PEI, with a comparably negative impact on QoL. QoL tools exist to assess PEI and its response to enzyme therapy; however, we hypothesise that PEI symptom scale scores will be unreliable in SSA-induced PEI due to the concurrent improvement of the carcinoid symptoms. Methods Adult patients commencing SSA therapy for NETs were recruited from December 2020. Qualitative assessments of the impact of SSAs and pancreatic exocrine function on patient QoL were performed before and during (at 8 weeks) therapy. The Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q) was used to capture patient-reported assessment of relevant symptoms. Health-related QoL was assessed using the European Organisation Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLC)-C30, supplemented by the EORTC GI.NET.21. Patients were specifically asked about steatorrhea at both assessments. Results Seven patients completed the study. 5-HIAA levels were raised in 4/7 patients, indicative of carcinoid syndrome, secondary to the NET. Pancreatic exocrine function reduced after SSA therapy in all patients (data reported elsewhere) but paradoxically PEI-Q symptom scale scores reduced (median decrease from baseline: -18.5%, range: -1.5- -55.6%; p = 0.018) (Figure 1). According to PEI-Q, all seven patients would meet the criteria for a mild PEI at baseline, and two would be considered severe. One patient reported steatorrhea after commencing SSA-therapy. No changes in relevant domains of EORTC questionnaires were statistically significant, including functional, symptomatic, and overall health scores. Conclusions The PEI-Q tool is not useful for assessing SSA-related PEI due to substantial symptom overlap with the tumour itself and SSA therapy. The decrease in symptom score is likely due to improvement of carcinoid syndrome, independent of PEI. Although the cardinal PEI symptom is steatorrhea, there is no distinction between that and diarrhoea in the EORTC tool, and confounding aetiologies of diarrhoea in NET patients may further complicate assessment. Current available QoL measures are of limited use in the setting of SSA-related PEI, and care should be taken if evaluating PEI or response of PEI to treatment.

Superinfection of other hepatitis viruses on top of chronic hepatitis B: The more, the worse

Superinfection of other hepatitis viruses on top of chronic hepatitis B: The more, the worse

Für welche Patienten und Patientinnen ist eine webbasierte psychotherapeutische Nachsorge nach psychosomatischer Rehabilitation am besten geeignet?

In order to maintain the effects achieved during the psychosomatic rehabilitation, according aftercare is indicated for most rehabilitation patients. Due to the current low supply of aftercare psychotherapists (so-called aftercare therapists) licensed by the German Pension Insurance web-based aftercare provides an equivalent alternative to analogue (in person) offers. This study clarifies which characteristics indicate that web-based aftercare is particularly recommended and how web-based formats are evaluated by participants, especially with regard to the therapeutic relationship. 142 psychosomatic rehabilitation patients were randomly assigned to analogue aftercare or web-based aftercare if a service close to their home was available (equivalence study design). Test variables were collected by questionnaires and analyzed stratified for age and gender. For male participants, there are no significant differences between the two aftercare formats. Women appear to have lower long-term depression scores when participating in web-based aftercare. Participants till the age 50 benefit significantly more from web-based aftercare than rehabilitants above age 50, The quality of the therapeutic relationship is rated equally well in both aftercare formats. Particularly in view of the increasing digitization of healthcare in times of the corona pandemic, web-based aftercare services offer the possibility of providing patients with aftercare independent of the availability of analogue-services and with the same benefits as analog therapies. Demographic factors such as age and sex must be taken into account when determining the indication. Therapists should recommend web-based aftercare especially for younger patients and for women, while men and older patients can be recommended both services equally. Therapists who offer web-based aftercare should be trained in advance on technical and content-related aspects, as was done in the present work.

C57. Left Main Coronary Artery Compression by A Dilatated Pulmonary Artery in Patients with Pulmonary Arterial Hypertension: What Should We Do?

Abstract Background Pulmonary artery hypertension (PAH) is often associated with angina and extrinsic compression of left main coronary artery (LMCA) by a dilatated pulmonary artery is recognized as the cause. The optimal management for pulmonary arterial hypertension with extrinsic LMCA compression has not been clearly established. Case Summary We report on 31-year-old female with secundum atrial septal defect and 44 -year-old female with incomplete atrioventricular septal defect complain of progressive typical angina that aggravated with exertion. The electrocardiogram showed right heart strain and chest radiograph showed cardiomegaly involving the right cavities with enlargement of the pulmonary arch. Right heart catheterization showed pulmonary arterial hypertension with the mean pulmonary artery pressure of 61 mmHg and 65 mmHg respectively. Cardiac CT demonstrated compression of proximal LMCA by dilatated pulmonary artery. Although with optimal phosphodiesterase-5 (PDE5) inhibitor and prostacyclin analog therapy, patients still complain of angina. Discussion LMCA compression may be associated with additional complications of severe myocardial ischemia, including myocardial infarction, left ventricle dysfunction, arrhythmia, and eventually, sudden death. It may occur in patients with PAH with severely dilated PA and can be identified with either computed tomographic coronary angiography or selective coronary angiography. Furthermore, there are no guidelines recommending optimal management of this disease entity. Optimalization of pharmacologic treatment of PAH may reduce compression-related symptoms. A stent implantation is a promising alternative option for the treatment of LMCA compression and provides an optimal risk-to-benefit ratio, both for symptom relief and for long-term outcomes.

C57. Left Main Coronary Artery Compression by A Dilatated Pulmonary Artery in Patients with Pulmonary Arterial Hypertension: What Should We Do?

Abstract Background Pulmonary artery hypertension (PAH) is often associated with angina and extrinsic compression of left main coronary artery (LMCA) by a dilatated pulmonary artery is recognized as the cause. The optimal management for pulmonary arterial hypertension with extrinsic LMCA compression has not been clearly established. Case Summary We report on 31-year-old female with secundum atrial septal defect and 44 -year-old female with incomplete atrioventricular septal defect complain of progressive typical angina that aggravated with exertion. The electrocardiogram showed right heart strain and chest radiograph showed cardiomegaly involving the right cavities with enlargement of the pulmonary arch. Right heart catheterization showed pulmonary arterial hypertension with the mean pulmonary artery pressure of 61 mmHg and 65 mmHg respectively. Cardiac CT demonstrated compression of proximal LMCA by dilatated pulmonary artery. Although with optimal phosphodiesterase-5 (PDE5) inhibitor and prostacyclin analog therapy, patients still complain of angina. Discussion LMCA compression may be associated with additional complications of severe myocardial ischemia, including myocardial infarction, left ventricle dysfunction, arrhythmia, and eventually, sudden death. It may occur in patients with PAH with severely dilated PA and can be identified with either computed tomographic coronary angiography or selective coronary angiography. Furthermore, there are no guidelines recommending optimal management of this disease entity. Optimalization of pharmacologic treatment of PAH may reduce compression-related symptoms. A stent implantation is a promising alternative option for the treatment of LMCA compression and provides an optimal risk-to-benefit ratio, both for symptom relief and for long-term outcomes.

Abstract PR-002: A phase II pilot trial of nivolumab (N) + albumin bound paclitaxel (AP) + paricalcitol (P) + cisplatin (C) + gemcitabine (G) (NAPPCG) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC)

Abstract Background: Effective therapy for the treatment of PDAC remains one of the greatest unmet oncology clinical needs. The addition of C to G and AP has shown 71% ORR in a previously reported study [JAMA Oncol. 2019 Oct 3;6(1):125-32]. In preclinical work, vitamin D (Vit D) analog therapy decreases myeloid derived suppressor cells and regulatory T cells, turning PDAC into a more immune favorable microenvironment. This trial combines AP/C/G with Vit D analog P and the anti-PD-1 antibody N as a combination therapy for patients with previously untreated metastatic PDAC. This trial evaluates the efficacy and safety of NAPPCG in that patient population (NCT02754726). Methods: Eligibility criteria include Stage IV PDAC, no prior chemotherapy for systemic disease, KPS ≥ 70, and RECIST 1.1 measurable disease. Doses are AP 125 mg/m2, G 1000 mg/m2, each infused over 30 minutes with C 25 mg/m2 infused over 60 minutes on days 1, 8, 22, and 29 of a 42-day cycle. N is given at a fixed dose of 240 mg as a 60 minute infusion on days 1, 15, and 29. P is given at a fixed dose of 25 µg IV twice weekly. Primary objective was to determine the efficacy of the combination for patients with previously untreated metastatic PDAC through determining CR, ORR, PFS, and OS. The secondary objective was to evaluate safety in patients with previously untreated metastatic PDAC. Exploratory endpoints include evaluating tissue molecular profile as it relates to treatment outcomes. Results: Trial was conducted May 2016 with enrollment completed August 2020. 35 patients have been enrolled in the study and 32 are evaluable (baseline and ≥1 follow up CT scan). Most common drug-related grade (Gr) 3-4 adverse events (AE’s), are thrombocytopenia 76% (gr 3 = 34%, gr 4 = 28%) with no serious bleeding events, anemia 37% (gr 3 = 37%, gr 4 = 0%), and CIPN 11% (gr 3 = 11%, gr 4 = 0%). Immune Related Adverse Events >5% were colitis (gr 3=8.6%, gr 4= 0%) and dermatitis (gr 3=8.6%, gr 4= 0%). By RECIST 1.1 criteria, the best response is 1 CR, 26 PR, 4 SD, 1 PD, yielding an 84% ORR (95% CI = (67%, 95%). Median PFS is 6 months (95% CI = (5, 8)). Median OS is 18 months (95% CI = (13, 22)). Conclusions: Although a small study, the high response rate is encouraging. Evaluation of exploratory endpoints is ongoing. Pursuing this regimen in localized PDAC is warranted due to its high ORR. Supported by grants from the Seena Magowitz Foundation, Mattress Firm, Bristol Myers Squibb, and SU2C. Citation Format: Erkut Borazanci, Gayle S. Jameson, Sunil Sharma, Frank Tsai, Ronald L. Korn, Lana Caldwell, Karen Ansaldo, David T. Ting, Denise Roe, Anna Bermudez, Daniel D. Von Hoff. A phase II pilot trial of nivolumab (N) + albumin bound paclitaxel (AP) + paricalcitol (P) + cisplatin (C) + gemcitabine (G) (NAPPCG) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC) [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PR-002.

Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study)

Functional cure, defined based on hepatitis B surface antigen (HBsAg) loss, is rare during nucleos(t)ide analogue (NA) therapy and guidelines on finite NA therapy have not been well established. We aim to analyze off-therapy outcomes after NA cessation in a large, international, multicenter, multiethnic cohort of patients with chronic hepatitis B (CHB). This cohort study included patients with virally suppressed CHB who were hepatitis B e antigen (HBeAg)-negative and stopped NA therapy. Primary outcome was HBsAg loss after NA cessation, and secondary outcomes included virologic, biochemical, and clinical relapse, alanine aminotransferase flare, retreatment, and liver-related events after NA cessation. Among 1552 patients with CHB, cumulative probability of HBsAg loss was 3.2% at 12 months and 13.0% at 48 months of follow-up. HBsAg loss was higher among Whites (vs Asians: subdistribution hazard ratio, 6.8; 95% confidence interval, 2.7-16.8; P < .001) and among patients with HBsAg levels <100 IU/mL at end of therapy (vs ≥100 IU/mL: subdistribution hazard ratio, 22.5; 95% confidence interval, 13.1-38.7; P < .001). At 48 months of follow-up, Whites with HBsAg levels <1000 IU/mL and Asians with HBsAg levels <100 IU/mL at end of therapy had a high predicted probability of HBsAg loss (>30%). Incidence rate ofhepatic decompensation and hepatocellular carcinoma was0.48 per 1000 person-years and 0.29 per 1000 person-years, respectively. Death occurred in 7/19 decompensated patients and 2/14 patients with hepatocellular carcinoma. The best candidates for NA withdrawal are virally suppressed, HBeAg- negative, noncirrhotic patients with CHB with low HBsAg levels, particularly Whiteswith <1000 IU/mL and Asians with <100 IU/mL. However, strict surveillance is recommended to prevent deterioration.

Virological breakthrough after immune checkpoint inhibitor and nucleos(t)ide analog treatment in patients with hepatitis B surface antigen positive hepatocellular carcinoma: a real-world study

BackgroundImmune checkpoint inhibitors (ICIs) have been shown to be a promising and effective treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, there is a lack of evidence-based data...

Seamless support from screening to anti-HCV treatment and HCC/ decompensated cirrhosis: Subsidy programs for HCV elimination.

Viral hepatitis poses a major public health problem in Japan. Chronic viral hepatitis is a progressive liver disease that eventually develops into liver cirrhosis and liver cancer. Since nucleic acid analog therapy for hepatitis B and interferon-free therapy for hepatitis C have made it possible to control the disease status or eliminate the viruses, it is very important that more people receive hepatitis virus tests to confirm the presence of infection at an early stage, and that patients with hepatitis detected by the tests receive appropriate medical care. Currently, the government of Japan is implementing comprehensive measures for hepatitis control based on five key strategies. Moreover, the goal listed in the Basic Guidelines on Hepatitis Measures is to reduce the frequency of progression of hepatitis to cirrhosis or liver cancer through a scheme consisting of testing people for hepatitis, getting those who test positive to visit a medical institution and receive treatment, and providing appropriate and high-quality hepatitis care through specialized medical institutions and regional core centers for the management of liver disease. To achieve the goal, various subsidy programs including an expense subsidy system for hepatitis treatment have been implemented in Japan. It is important for healthcare professionals to have sufficient knowledge of public support for efficient hepatitis C virus (HCV)-related liver disease detection and care.

The Combination of Oral PDE5-Inhibitor (Sildenafil) And Oral Prostacy- clin Analogue (Beraphrost) Therapy for Increasing Quality of Life in Adults with Pulmonary Arterial Hypertension Related to Uncorrected Secundum Atrial Septal Defect

Background : Sildenafil, an oral phosphodiesterase type-5 inhibitor, has vasodilatory effects through a cyclic guanosine 3,5-monophosphate–dependent mechanism, whereas beraprost, an oral prostacyclin analog, induces vasorelaxation through a cAMP-dependent mechanism. This combination has often used but there was little detailed study on it Objectives : To investigate whether the combination of oral sildenafil and beraprost is superior to sildenafil alone in in adult patients with Pulmonary Arterial Hypertention (PAH) related uncorrected secundum Atrial Septal Defect (ASD). Methods : Patients with secundum ASD who developed PAH divided into two group. Group A received oral sildenafil 3x40 mg and oral beraphrost 3x20 mcg. Group B received oral sildenafil only 3x40 mg in a 12-week. Health-related quality of life (HRQoL) was recorded by patients using the Medical Outcomes Study 36-item short form (SF-36) questionnaires at baseline and after 12 of therapy. Therapy adherence was achieved through a series of phone calls and a four-weekly hospital visit. Every normal follow-up appointment included an examina- tion of side effects and a dosage modification based on the clinical situation Results: We didn’t found any significant of proportion different in cofounding factor between groups. Compared with Group B, Group A had better functional capacity, limitation to physical health, energy fatigue, pain, and health change (P=0.00, P=0.03, P=0.044, P=0.026, P=0.008, respectively). Conclusion: Combination between oral sildenafil therapy 40 mg three times per day and beraphrost 20 mcg two times per day significantly increase the HRQoL in PAH patients in uncorrected secundum ASD compared sildena- fil alone

Cessation of Nucleos(t)ide Analogue Therapy in Non-Cirrhotic Hepatitis B Patients with Prior Severe Acute Exacerbation.

Chronic hepatitis B (CHB) with severe acute exacerbation (SAE) is an urgent problem requiring nucleos(t)ide analogue (NA) therapy. We aim to evaluate the clinical relapse (CR) risk after discontinuing NA in patients with prior SAE. Methods: In this retrospective cohort study, CHB patients who discontinued NA therapy were screened between October, 2003 and January, 2019. A total of 78 non-cirrhotic patients who had received NA therapy for CHB with SAE, i.e., bilirubin ≥ 2 mg/dL and/or prothrombin time prolongation ≥3 s, (SAE group) were matched 1:2 with 156 controls without SAE (non-SAE group) by means of propensity scores (age, gender, NA categories, NA therapy duration, and HBeAg status). Results: The 5-year cumulative incidences of severe CR, i.e., ALT > 10X ULN, (42.78%, 95% CI: 27.84–57.73% vs. 25.42%, 95% CI: 16.26–34.58%; p = 0.045) and SAE recurrence (25.91%, 95% CI: 10.91–40.91% vs. 1.04%, 95% CI: 0–3.07%; p < 0.001) were significantly higher in the SAE group. Prior SAE history (HR 1.79, 95% CI: 1.04–3.06) was an independent factor for severe CR. The 5-year cumulative incidence of HBsAg seroclearance was significantly higher in the SAE group than that in the non-SAE group (16.82%, 95% CI: 2.34–31.30% vs. 6.02%, 95% CI: 0–13.23%; p = 0.049). Conclusions: Even though it creates a greater chance of HBsAg seroclearance, NA therapy cessation may result in a high risk of severe CR in non-cirrhotic CHB patients with prior SAE.

Association of Virological Response to Antiviral Therapy With Survival in Intermediate-Stage Hepatitis B Virus-Related Hepatocellular Carcinoma After Chemoembolization.

IntroductionRole of response to antiviral therapies on survival of patients with intermediate-stage hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) undergoing transarterial chemoembolization (TACE) remains unknown. We aimed to determine whether virological response (VR) or prolonged maintained virological response (MVR) to nucelos(t)ide analogues (NA) therapy could result in improved survival in HBV-HCC patients receiving TACE.MethodsBetween January 2012 and October 2018, data of patients with intermediate HBV-HCC who underwent TACE and started NA therapy within one week prior to TACE treatment at our institution were reviewed. Overall survival (OS) was compared using the Kaplan-Meier method with log-rank test between different VR status groups. Univariable and multivariable Cox regression analyses were used to determine the association between achievement of VR or MVR and OS. VR was defined as an undetectable HBV DNA level (<100 IU/ml) on two consecutive measurements during NA treatment. MVR was defined as a persistently undetectable HBV DNA level after achieving a VR.ResultsA total of 1265 patients undergoing TACE with a median follow-up time of 18 months (range, 2-78 months) were included in the analysis. Of 1265 NA-treated patients [1123 (88.8%) male, median (range) age, 56 (18-75) years], 744 patients (58.8%) achieved VR and the remaining patients (41.2%) did not. Patients with achievement of VR showed a significantly longer OS than those without VR (median OS: 21 vs 16 months; HR, 0.707; 95% CI, 0.622-0.804; P<0.001). Among patients with VR, MVR was present in 542 patients (72.8%), while the other 202 patients (27.2%) in the non-MVR group. The OS for the MVR group was significantly higher than the non-MVR group (median OS: 23.2 vs 18 months; HR, 0.736; 95% CI, 0.612-0.885; P=0.001). Additionally, patients with MVR status more than two years showed a better OS than those with just one-year (HR, 0.719; 95% CI, 0.650-0.797; P<0.001) or one-to-two-year MVR (HR, 0.612; 95% CI, 0.471-0.795; P=0.024). On multivariable analyses, splenomegaly and up-to-seven criteria were independent prognostic factors of OS in both VR and MVR cohorts.ConclusionsIn patients with intermediate-stage HBV-HCC, both VR to antiviral therapy and prolonged response are associated with prolonged OS after TACE, especially for those within up-to-seven criteria.

Determinants of re-compensation in patients with hepatitis B virus-related decompensated cirrhosis starting antiviral therapy.

Despite antiviral therapy, liver function often fails to recover in patients with hepatitis B virus (HBV)-related decompensated cirrhosis. To establish a prognostic model to predict re-compensation in patients starting potent nucleos(t)ide analogue (NUC) therapy METHODS: We analysed 311 consecutive patients with HBV-related decompensated cirrhosis treated with entecavir or tenofovir. The primary outcome was re-compensation, defined as recovery to a Child-Pugh score of 5. The BC2AID score was developed from a cohort of 152 subjects based on competing risk models and validated in another cohort of 159 subjects. Re-compensation occurred in 57.2% and 66.7% of the subjects in the derivation and validation cohorts, respectively. Six independent predictors for re-compensation were identified in the derivation cohort and these comprised the BC2AID score: bilirubin ≤5mg/dL (adjusted sub-distribution hazard ratio [aSHR] 2.18), absence of severe complications (aSHR 2.78), alpha-fetoprotein (AFP) ≥50ng/mL (aSHR 2.54), alanine aminotransferase ≥200IU/L (aSHR 2.62), international normalised ratio ≤1.5 (aSHR 2.37) and ≤6months from initial decompensation until initiation of NUCs (aSHR 4.79). In the validation cohort, the area under the receiver operating characteristic curve of the BC2AID score for re-compensation within 1year of NUC therapy was significantly higher than that of the Child-Pugh, MELD, MELDNa and BE3A scores (0.813 vs 0.691, 0.638, 0.645 and 0.624, respectively; all P<0.05). Six clinical parameters, including AFP and the timing of antiviral therapy, were combined into a scoring system to accurately predict early re-compensation in patients with HBV-related decompensated cirrhosis.

ADVANCES IN THE NEUROSURGICAL AND COMBINED TREATMENT OF PATIENTS WITH ACROMEGALY

Aim. The study was carried out to identify and analyze the factors of a positive outcome of surgical and radiation treatment of acromegaly. Methods. The work was performed on clinical material and summarizes treatment results of 256 patients (90 males and 166 females). 86% of patients underwent surgical treatment, 14% of patients received radiation therapy during 2002–2018. Significance of factors of a positive outcome of treatment was carried out using the RStudio program. Results. The results of the study revealed that: 1. Significant factors (p &lt;0.05) of a positive outcome of surgical treatment of acromegaly are somatostatin analogs (SSA) therapy before surgery, a small tumor size (microadenomas), and the absence of extrasellar tumor spread. 2. The most significant factor in achieving remission of acromegaly after non-radical adenomectomy is postoperative therapy with SSA (p &lt;0.05). 3. Aggressive pituitary tumors invading surrounding structures, high baseline IGF-1 levels, unfavorable histological findings, macroadenomas, growth hormone levels above 10 μg/L before therapy, and extrasellar tumor spread were associated with less favorable outcomes of acromegaly radiation therapy (RT) (p &lt;0.05). The most significant factor in achieving remission of acromegaly is SSA therapy after RT (p &lt;0.05). Conclusion. Surgical treatment is the optimal primary treatment for acromegaly. Drug therapy with SSA is effective and the preferred treatment after non-radical surgery.

Gonadotropin releasing hormone analogue treatment of central precocious puberty is not associated with altered prevalence of polycystic ovary syndrome: a single center cohort study

BackgroundThere is conflicting evidence regarding an association between gonadotropin releasing hormone analogue (GnRHa) therapy and polycystic ovary syndrome (PCOS). This study aimed to compare the prevalence of endocrine disorders, primarily PCOS, between women who had been treated with GnRHa for central precocious puberty (CPP) and those who were not treated.MethodsThis was a retrospective cohort study, including women diagnosed with central precocious puberty between 1989 and 2011 in a university affiliated tertiary medical center. Data collected included demographic data, medical background, clinical presentation at diagnosis and duration of treatment (zero for non-treated). Gynecologic and endocrine long-term outcomes were compared by treatment group.ResultsFifty-one women were included in the study, 27/51 had been treated with gonadotropin releasing hormone analogue (GnRHa). Overall prevalence of PCOS was 19.6%. No statistically significant difference in prevalence of PCOS was demonstrated between the treated and non-treated groups. Similarly, overall prevalence of either clinical or laboratory hyper-androgenism, was 29.4% and 33.3%, for the treatment and non-treatment groups respectively (p = non-significant).ConclusionsGnRHa treatment for precocious puberty is not associated with increased risk of polycystic ovary syndrome.

The Impact of Nucleos(t)ide Analogs Off-Therapy Among Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis.

Background and Aim: Although most chronic hepatitis B (CHB) patients achieve effective virological suppression after receiving long-term nucleos(t)ide analogs (Nucs) therapy, the safety of off-therapy is controversial under the monitor.Methods: We identified studies through searching PubMed, Embase, Cochrane Library, and Web of Science from January 1990 to February 2021. The eligible studies compare the long outcomes between discontinued and continued Nucs treatments groups among CHB patients. This study was conducted to investigate long-term outcomes, including biochemical, serological, and virological outcomes, as well as hepatocellular carcinoma (HCC) development rate between discontinued and maintained Nucs therapy groups among CHB patients.Results: Five eligible studies covering 1,425 patients were selected for meta-analysis. Our result exhibits that patients with Nucs off-treatment have a higher risk of alanine aminotransferase (ALT) flares-up than those who continued Nucs therapy under the monitor (OR = 9.39, 95%CI = 3.87–22.78). Nucs off-therapy patients have a higher virological bound incidence (OR = 617.96, 95%CI = 112.48–3,395.14) and a higher HBV DNA level (OR = 9.39, 95%CI = 3.87–22.78) than those who continued Nucs therapy. There was no statistically significant difference in the risk of hyperbilirubinaemia, hepatic decompensation, and HCC development between both two groups. Patients in Nucs off-therapy group demonstrate a higher HBsAg loss rate than those in the continued group (OR = 7.10, 95%CI = 6.68–13.69).Conclusions: Nucs off-therapy patients may exhibit a higher chance of achieving HBsAg loss than those who continue Nucs therapy. It requires close monitoring after Nucs off-therapy and timely restarting of Nucs therapy when ALT concentrations increase.

Effectiveness and predictors of response to somatostatin analogues in patients with gastrointestinal angiodysplasias: a systematic review and individual patient data meta-analysis

Gastrointestinal angiodysplasias are vascular malformations that often cause red blood cell transfusion-dependent anaemia. Several studies suggest that somatostatin analogues might decrease rebleeding rates, but the true effect size is unknown. We therefore aimed to investigate the efficacy of somatostatin analogues on red blood cell transfusion requirements of patients with gastrointestinal angiodysplasias and to identify subgroups that might benefit the most from somatostatin analogue therapy. We did a systematic review and individual patient data meta-analysis. We searched MEDLINE, Embase, and Cochrane on Jan 15, 2016, with an updated search on April 25, 2021. All published randomised controlled trials and cohort studies that reported on somatostatin analogue therapy in patients with gastrointestinal angiodysplasias were eligible for screening. We excluded studies without original patient data, single case reports, small case series (ie, <10 participants), studies in which patients had a specific aetiology of gastrointestinal angiodysplasias, and studies in which somatostatin analogue therapy was initiated simultaneously with other treatment modalities. Authors of eligible studies were invited to share individual patient data. Aggregated data was used if individual patient data were not provided. The primary outcome was the mean reduction in the number of red blood cell transfusions during somatostatin analogue therapy, compared with baseline, expressed as the incidence rate ratio (IRR) and absolute mean decrease. We defined patients as either good responders (≥50% reduction in the number of red blood cell transfusions) or poor responders (<50% reduction). A mixed-effects negative binomial regression was used to account for clustering of patients and skewness in data. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42020213985. We identified 11 eligible studies (one randomised controlled trial and ten cohort studies) of moderate-to-high quality and obtained individual patient data from the authors of nine (82%) studies. The remaining two (18%) studies provided sufficient information in the published manuscript to extract individual patient data. In total, we analysed data from 212 patients. Somatostatin analogues reduced the number of red blood cell transfusions with an IRR of 0·18 (95% CI 0·14-0·24; p<0·0001) during a median treatment duration of 12 months (IQR 6·0-12·0) and follow-up period of 12 months (12·0-12·0), correlating with a mean absolute decrease in the number of red blood cell transfusions from 12·8 (95% CI 10·4-15·8) during baseline to 2·3 (1·9-2·9) during follow-up-ie, a reduction of 10·5 red blood cell transfusions (p<0·0001). 177 (83%) of 212 patients had a good response to somatostatin analogue therapy (defined as at least a 50% reduction in the number of red blood cell transfusions). Heterogeneity across studies was moderate (I2=53%; p=0·02). Location of gastrointestinal angiodysplasias in the stomach compared with angiodysplasias in the small bowel and colon (IRR interaction 1·92 [95% CI 1·13-3·26]; p=0·02) was associated with worse treatment response. Octreotide was associated with a better treatment response than lanreotide therapy (IRR interaction 2·13 [95% CI 1·12-4·04]; p=0·02). The certainty of evidence was high for the randomised controlled trial and low for the ten cohort studies. Adverse events occurred in 38 (18%) of 212 patients receiving somatostatin analogue therapy, with ten (5%) discontinuing this therapy because of adverse events. The most common adverse events were loose stools (seven [3%] of 212), cholelithiasis (five [2%]), flatulence (four [2%]), and administration site reactions (erythema, five [2%]). Somatostatin analogue therapy is safe and effective in most patients with red blood cell transfusion-dependent bleeding due to gastrointestinal angiodysplasias. Somatostatin analogue therapy is more effective in patients with angiodysplasias located in the small bowel and colon, and octreotide therapy seems to be more effective than lanreotide therapy. The Netherlands Organisation for Health Research and Development and the Radboud University Medical Center.