Single-operator cholangioscopy unveiling a pinehole post-cholecystectomy biliary strictures.

77-year-old female with history of cholecystectomy was admitted at emergency department with fever and myalgia, without other complaints. Physical examination revealed fever, and laboratory tests indicated cholestasis (total bilirubin: 1.5xULN, glutamyltransferase: 20xULN, alkaline phosphatase: 5xULN). Computed Tomography revealed common bile duct (CBD) dilation (9mm), with suspected choledocholithiasis. Given the diagnosis of acute cholangitis, antibiotics were started and ERCP was performed. ERCP revealed a short CBD stenosis (< 2mm length), close to surgical clip, with upstream dilation of the CBD; an 8mm stone in the distal CBD was observed and successfully removed. As guidewire advancement failed after multiple attempts, a SpyGlass DS cholangioscopy was performed showing a fibrotic pinehole stenosis. Guidewire was passed through the stenosis under direct visualization, and an 80-mmx10mm fully covered metal stent deployed.

Intrabiliary metastasis of colorectal adenocarcinoma: the SPY perspective.

We report a case of a 54-year-old female that underwent sigmoidectomy for stage IIA adenocarcinoma. After 5 years of follow-up, despite normal colonoscopy and CEA and CA-19.9 levels, abdominal CT revealed a 3 cm perianastomotic peritoneal lesion and suspected liver metastasis. Although liver biopsy was negative for malignancy, the perianastomotic lesion was confirmed to be metastasis of colonic adenocarcinoma. After chemotherapy, a mild elevation of alkaline phosphatase and γ-GT was evident. MRCP revealed dilation of intrahepatic bile ducts in segment VIII due to an intraluminal lesion in the right hepatic duct, suggestive of intraductal cholangiocarcinoma.

Duodenal lipoma - An unusual finding, location and presentation.

An 82-year-old man was admitted for acute cholangitis. He presented with jaundice and elevated hepatic cholestasis enzymes and C-reactive protein. Abdominal ultrasound and CT scan showed no evidence of gallstones and the main bile duct had 6 mm of diameter. Broad-spectrum antibiotic therapy was initiated and the patient was referred for Endoscopic Retrograde Cholangiopancreatography. During duodenoscopy, a pedunculated subepithelial lesion, measuring approximately 20-30 mm, and suggestive of being a lipoma was found, obstructing the papillary orifice and preventing its access. It was then removed using a diathermic snare. Subsequent cholangiography confirmed the absence of gallstones or any other cause of biliary obstruction. Histopathological analysis confirmed that the lesion was a duodenal lipoma. The patient evolved favorably and had no subsequent episodes of jaundice or cholangitis during follow-up.

Paraneoplasic Behçet's Syndrome associated with Chronic Myeloid Leukemia.

A 49-year-old man presented with a three-week history of abdominal pain, bloody diarrhoea and fever. Reported oral ulcers, weight loss and asthenia, as well as papulo-pustular lesions on his limbs and a recurrent ulcer in the lip (Fig.1) in the previous year. During hospitalization, he developed pathergy at venipuncture sites and painful scrotum ulcers. Laboratory showed pancytopenia and elevated CRP. Viral and autoimmune tests were negative. Abdominal CT revealed thickening of the ileocecal region with adenopathies. Blood smear and myelogram were compatible with Chronic Myeloid Leukemia (CML). Bone marrow culture and BK were negative. Karyotype revealed no changes, namely, no trisomy of the 8th. Ileocolonoscopy revealed aphthoid erosions of the ileocecal mucosa and ovoid punched-out cecal ulcers. Biopsies showed intense chronic inflammation in the lamina propria and submucosa with erosions and ulcers. Thus, presenting 5 points in the International Criteria for Behçet's Disease, this diagnosis was assumed as a paraneoplastic manifestation of CML. Corticosteroids improved symptoms, but the patient died three weeks later due to a blastic crisis. BS has been reported in association with CML, some concurrent with, or following treatment with interferon-a or hydroxyurea. Although the pathogenesis remains unclear, there is increasing awareness of its link to hematological malignancies, and trisomy of the 8th.

Factors Influencing Performance of Cholangioscopy-Guided Lithotripsy Including Available Different Technologies: A Prospective Multicenter Study with 94 Patients.

BACKGROUND: Peroral cholangioscopy (POC)-guided lithotripsy is an effective treatment for difficult biliary stones. A clear definition of factors associated with the efficacy of POC-guided lithotripsy in one session and the performance of electrohydraulic lithotripsy (EHL) and laser lithotripsy (LL) have not clearly emerged. METHODS: This was a non-randomized prospective multicenter study of all consecutive patients who underwent POC lithotripsy (using EHL and/or LL) for difficult biliary stones. The primary endpoint of the study was the number of sessions needed to achieve complete ductal clearance and the factors associated with this outcome. Secondary endpoints included the evaluated efficacies of LL and EHL. RESULTS: Ninety-four patients underwent 113 procedures of EHL or LL. Complete ductal clearance was obtained in 93/94 patients (98.94%). In total, 80/94 patients (85.11%) achieved stone clearance in a single session. In the multivariate analysis, stone size was independently associated with the need for multiple sessions to achieve complete ductal clearance (odds ratio = 1.146, 95% confidence interval: 1.055-1.244; p = 0.001). Using ROC curves and the Youden index, 22 mm was found to be the optimal cutoff for stone size (95% confidence interval: 15.71-28.28; p < 0.001). The majority of the patients (62.8%) underwent LL in the first session. Six patients failed the first session with EHL after using two probes and therefore were crossed over to LL, obtaining ductal clearance in a single additional session with a single LL fiber. EHL was significantly associated with a larger number of probes (2.0 vs. 1.02) to achieve ductal clearance (p < 0.01). The mean procedural time was significantly longer for EHL than for LL [72.1 (SD 16.3 min) versus 51.1 (SD 10.5 min)] (p < 0.01). CONCLUSIONS: POC is highly effective for difficult biliary stones. Most patients achieved complete ductal clearance in one session, which was significantly more likely for stones < 22 mm. EHL was significantly associated with the need for more probes and a longer procedural time to achieve ductal clearance.

Needle knife fistulotomy in flat and diverticular papillae: Is it time for redemption?

BACKGROUND: European Society of Gastrointestinal Endoscopy (ESGE) recommends needle-knife fistulotomy (NKF) as the preferred precut technique in cases when standard cannulation techniques fail. Despite scarce scientific evidence, flat and diverticular papillae are thought not to be ideal for NKF, as they are associated with poor outcomes. The present study aimed to determine the outcomes of the use of NKF in relation to flat and intradiverticular papillae. METHODS: This prospective multicenter study enrolled consecutive patients, evidencing naïve flat (group A, n = 49) or diverticular papilla (group B, n = 28), who underwent NKF after failure of standard cannulation techniques. Diverticular morphology was subdivided into intradiverticular (group B1, n = 14) and diverticular border papillae (group B2, n = 14), using a previously validated endoscopic classification of the major papilla. The success of biliary cannulation at initial endoscopic retrograde cholangiopancreatography (ERCP), overall biliary cannulation, overall cannulation time, and the rate of adverse events were assessed in the study. RESULTS: The initial cannulation rates were 93.9%, 64.3% and 71.4% for group A, B1, and B2, respectively (P = 0.005); overall cannulation rates after a second ERCP were 98.0%, 92.9% and 85.7%, respectively (P = 0.134). Adverse events occurred in 11.7% of patients, with post-ERCP pancreatitis (PEP) being the most common adverse event (10.4%). Although there was a trend towards a higher incidence of PEP in flat papillae, univariate and multivariate analyses did not show any significant relationship between pancreatitis and trainee involvement, papillary morphology, nor overall cannulation time. CONCLUSIONS: Although flat papillae are associated with high success rates of biliary cannulation using NKF, the rate of PEP is not negligible. NKF is feasible in diverticular papillae, but it is associated with a modest success rate in the initial ERCP.

Outcomes of single-endoscopist-performed needle-knife fistulotomy for selective biliary access in 842 consecutive patients: learning curve and changes over a 14-year period in a retrospective study.

BACKGROUND AND AIMS: Needle-knife fistulotomy (NKF) has emerged as the preferred precut technique. From a late strategy, NKF has shifted to an early rescue technique and has been used recently as a primary method for biliary access. It is unknown how these changes have affected NKF outcomes. We analyzed the outcomes of NKF over time in a large cohort of patients. METHODS: Multicenter retrospective cohort study of 842 patients who underwent NKF for biliary access between 2006 and 2019. Patients were divided into four study periods according to a late or early cannulation strategy and to the use of post-ERCP pancreatitis prophylaxis (Period 1-Period 4). We assessed outcomes of NKF, learning curves and shifts over time. RESULTS: Bile duct access was obtained in 88.0% of the patients. The initial cannulation rate increased significantly from 77.5% in P1 to 92.0% in P4 (p < .001). An endoscopist can obtain 80% success rate after performing 100 NKF procedures (95% CI: 0.79-0.86) and a 95% success rate after 830 procedures (95% CI: 0.92-0.98). Adverse events and pancreatitis were observed in 6.5% and 4.9% of patients respectively. The rate of pancreatitis was not significantly different during the 4 periods (p = .190). A decline in the pancreatitis rate was observed from 2006 until 2016 (no trainees) and then an increase until 2019 (trainees involved). The presence of trainees increased the rate of pancreatitis in the last period by 9.9%. CONCLUSIONS: The success of NKF has increased significantly over the years, initially in a rapid manner and then more slowly. It is associated with a low rate of complications, which tend to decrease with experience. The involvement of trainees is associated with an increased rate of pancreatitis.

Kek-6: A truncated-Trk-like receptor for Drosophila neurotrophin 2 regulates structural synaptic plasticity.

Neurotrophism, structural plasticity, learning and long-term memory in mammals critically depend on neurotrophins binding Trk receptors to activate tyrosine kinase (TyrK) signaling, but Drosophila lacks full-length Trks, raising the question of how these processes occur in the fly. Paradoxically, truncated Trk isoforms lacking the TyrK predominate in the adult human brain, but whether they have neuronal functions independently of full-length Trks is unknown. Drosophila has TyrK-less Trk-family receptors, encoded by the kekkon (kek) genes, suggesting that evolutionarily conserved functions for this receptor class may exist. Here, we asked whether Keks function together with Drosophila neurotrophins (DNTs) at the larval glutamatergic neuromuscular junction (NMJ). We tested the eleven LRR and Ig-containing (LIG) proteins encoded in the Drosophila genome for expression in the central nervous system (CNS) and potential interaction with DNTs. Kek-6 is expressed in the CNS, interacts genetically with DNTs and can bind DNT2 in signaling assays and co-immunoprecipitations. Ligand binding is promiscuous, as Kek-6 can also bind DNT1, and Kek-2 and Kek-5 can also bind DNT2. In vivo, Kek-6 is found presynaptically in motoneurons, and DNT2 is produced by the muscle to function as a retrograde factor at the NMJ. Kek-6 and DNT2 regulate NMJ growth and synaptic structure. Evidence indicates that Kek-6 does not antagonise the alternative DNT2 receptor Toll-6. Instead, Kek-6 and Toll-6 interact physically, and together regulate structural synaptic plasticity and homeostasis. Using pull-down assays, we identified and validated CaMKII and VAP33A as intracellular partners of Kek-6, and show that they regulate NMJ growth and active zone formation downstream of DNT2 and Kek-6. The synaptic functions of Kek-6 could be evolutionarily conserved. This raises the intriguing possibility that a novel mechanism of structural synaptic plasticity involving truncated Trk-family receptors independently of TyrK signaling may also operate in the human brain.

Endometriosis of the Bladder: Clinical and Surgical Outcomes after Laparoscopic Surgery.

BACKGROUND/AIMS: Urinary tract endometriosis is rare. The bladder is the most common site affected. The nonspecific symptoms can make a diagnosis difficult. The aim of this study was to evaluate the clinical and surgical outcomes in women who underwent surgical treatment for bladder endometriosis (BE). METHODS: Ten patients who underwent surgical treatment for BE from January 2012 to November 2016 were retrospectively reviewed. Pre- and postoperative data, intraoperative findings, type of surgical procedure, and intra- and postoperative complications were analyzed. RESULTS: Two women were treated by laparoscopic shaving of the bladder lesion and 8 underwent laparoscopic partial cystectomy. Simultaneous resection of coexisting pelvic nodules was performed. No conversions to laparotomy were observed. There was only one intraoperative complication. No major or minor postoperative complications were observed and none of the patients required repeated interventions. Improvements in clinical symptoms were reported and there was no increase in long-term urinary frequency after surgery. There was 1 case of urinary symptom recurrence. CONCLUSION: Laparoscopic partial cystectomy and shaving of the bladder lesion seem to improve urinary symptoms, with a low rate of intra- and postoperative complications and a low rate of recurrence, without affecting long-term bladder capacity. This surgical approach requires an experienced gynecologist and urologist team.

Prolactinoma and pregnancy - a series of cases including pituitary apoplexy.

The objective of this article is to evaluate the impact of pregnancy in women with prolactinoma, the possible consequences of therapy maintenance/discontinuation during pregnancy and to assess the type of delivery and maternal-foetal obstetrical outcome. A retrospective study of all pregnant women with prolactinoma in our Centre between 2006 and 2014 was made. We had 35 cases of pregnant women with prolactinoma, two of which had an episode of pituitary apoplexy during the second trimester. At the time of conception, most women were being treated with 5 mg bromocriptine. The majority of women had suspended medication in the 8th week of gestation. Caesarean rate was 48.6%. The maternal foetal outcome was favourable in all cases.

Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial.

BACKGROUND: The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was designed to assess the effectiveness of a pneumococcal vaccine containing ten serotype-specific polysaccharides conjugated to Haemophilus influenzae protein D, tetanus toxoid, and diphtheria toxoid as the carrier proteins (PHiD-CV10) against invasive pneumococcal disease. METHODS: In this cluster-randomised, double-blind trial, children aged younger than 19 months received PHiD-CV10 in 52 clusters or hepatitis vaccines as control in 26 clusters. Infants aged younger than 7 months at the first vaccination received either a 3+1 or a 2+1 vaccination schedule, children aged 7-11 months received a 2+1 schedule, and those 12-18 months of age received a two-dose schedule. The primary and secondary objectives were to assess vaccine effectiveness against culture-confirmed invasive pneumococcal disease due to any of the ten vaccine serotypes for the 3+1 and 2+1 schedules, respectively, in children who received at least one PHiD-CV10 dose before 7 months of age. Masked follow-up of pneumococcal disease lasted from the first vaccination (from February, 2009, to October, 2010) to January 31, 2012. Invasive disease data were retrieved from data accumulated in the national infectious diseases register. This trial and the nested acute otitis media trial are registered with ClinicalTrials.gov, numbers NCT00861380 and NCT00839254, respectively. FINDINGS: 47,369 children were enrolled from February, 2009, to October, 2010. 30,528 participants were assessed for the primary objective. 13 culture-confirmed vaccine-type cases of invasive pneumococcal disease were detected: none in the PHiD-CV10 3+1 group, one in the PHiD-CV10 2+1 group, and 12 in the control groups. The estimates for vaccine effectiveness were 100% (95% CI 83-100) for PHiD-CV10 3+1 and 92% (58-100) for PHiD-CV10 2+1 groups. Two cases of any culture-confirmed invasive disease irrespective of serotype were detected in combined PHiD-CV10 infant cohorts compared with 14 in the corresponding control cohorts (vaccine effectiveness 93%, 75-99). In catch-up cohorts, seven cases of invasive disease were reported, all in the control group: two cases in the children enrolled at 7-11 months of age; and five cases in children enrolled at 12-18 months of age (vaccine effectiveness 100%, 79-100). Non-fatal serious adverse events suspected to be vaccine-related were reported via routine post-immunisation safety surveillance in 18 children. INTERPRETATION: This nationwide trial showed high PHiD-CV10 effectiveness against invasive pneumococcal disease when given in different schedules. For the first time, effectiveness of a 2+1 schedule in infants was confirmed in a clinical trial. FUNDING: GlaxoSmithKline Biologicals SA and National Institute for Health and Welfare, Finland.

Maternal Hypertriglyceridemia in Gestational Diabetes: A New Risk Factor?

Elevated maternal triglycerides (TGs) have been associated with excessive fetal growth. However, the role of maternal lipid profile is less studied in gestational diabetes mellitus (GDM). We aimed to study the association between maternal lipid profile in the third trimester and the risk for large-for-gestational-age (LGA) newborns in women with GDM. We performed an observational and retrospective study of pregnant women with GDM who underwent a lipid profile measurement during the third trimester. We applied a logistic regression model to assess predictors of LGA. A total of 100 singleton pregnant women with GDM and third-trimester lipid profile evaluation were included. In the multivariate analysis, pre-pregnancy BMI (OR 1.19 (95% CI 1.03-1.38), p = 0.022) and hypertriglyceridemia (OR 7.60 (1.70-34.10), p = 0.008) were independently associated with LGA. Third-trimester hypertriglyceridemia was found to be a predictor of LGA among women with GDM, independently of glycemic control, BMI, and pregnancy weight gain. Further investigation is needed to confirm the role of TGs in excessive fetal growth in GDM pregnancies.

EUS-Guided Choledochoduodenostomy after Failed Endoscopic Retrograde Cholangiopancreatography in Distal Malignant Biliary Obstruction.

Introduction: Malignant biliary obstruction drainage is essential, since jaundice is associated with morbidity and mortality. Endoscopic retrograde cholangiopancreatography (ERCP) is the recommended procedure for biliary drainage, with percutaneous biliary drainage being the classic alternative in cases of unsuccessful ERCP. Recently, endoscopic ultrasound-guided biliary drainage has been emerged as a new option, with EUS-guided choledochoduodenostomy (EUS-CDS) being considered an effective and safe method in the drainage of distal obstructions of the common bile duct. Aim: The aim of the study was to evaluate the efficacy and safety of EUS-CDS performed in patients with distal malignant biliary obstructions, after failed ERCP. Methods: Single-center retrospective cohort study between July 2017 and June 2022 including all consecutive patients submitted to EUS-CDS in our center. The primary outcomes were "technical success" and "clinical success," defined as "resolution of jaundice or improvement in total serum bilirubin level above 50% at 7th day and above 75% at 30th day after the procedure." Secondary outcomes were procedure-related adverse events, endoscopic reintervention, and survival time. Results: EUS-CDS was performed in 20 patients (65.0% male; median age 76 years). The most frequent etiology for the biliary obstruction was pancreatic adenocarcinoma (n = 17; 85.0%), and most patients presented at advanced stages of cancer (12/60% in stages III or IV). ERCP failure was mainly due to the presence of obstruction in the duodenal lumen (n = 11; 55.0%). Fully covered metallic stents were used in all patients, mostly HotAxiosTM (n = 15; 75.0%). The technical success rate was 100%, and the clinical success rate was 89.5% (n = 17/19) at 7th day and 93.3% (n = 14/15) at 30th day. Four patients (20.0%) developed cholangitis within the first 30 days after the procedure; there were no late complications, and no patient died as a complication of the procedure. In 2 patients (10.0%), endoscopic reintervention was necessary due to stent migration, incidentally detected. Median survival was 93 days (minimum 5-maximum 751). Conclusion: EUS-CDS was effective in biliary decompression of malignant obstructions of the common bile duct, with high clinical success and a favorable safety profile.

Introdução: A drenagem das obstruções biliares malignas é essencial, uma vez que a icterícia está associada a morbimortalidade. A colangiopancreatografia retrógrada endoscópica (CPRE) é o procedimento recomendado para a drenagem biliar, sendo a drenagem biliar percutânea (DBP) a alternativa clássica, se verificado insucesso. Recentemente, a drenagem da via biliar guiada por ecoendoscopia tem-se apresentado como uma nova opção, sendo a coledocoduodenostomia guiada por ecoendoscopia (CGE) considerado um método eficaz e seguro na drenagem de obstruções da via biliar distal. Objetivo: Avaliar o sucesso técnico e clínico e a segurança da CGE em doentes com obstrução da via biliar distal, após falência da CPRE. Métodos: Estudo de coorte retrospetivo, entre Julho/2017 e Junho/2022, de todos os doentes submetidos a CGE no nosso centro. Determinaram-se como outcomes primários o "sucesso técnico" e o "sucesso clínico" ("melhoria ≥50% na bilirrubinemia ao 7.º e ≥ 75% ao 30.º dias após o procedimento"). Os outcomes secundários incluíram a frequência de eventos adversos, necessidade de reintervenção e taxa de sobrevida. Foram utilizadas curvas de Kaplan-Meier para descrever a sobrevida. Resultados: A CGE foi realizada em 20 doentes (65.0% do sexo masculino; idade mediana 76 anos). A etiologia mais frequente para a obstrução foi o adenocarcinoma pancreático (n = 17; 85.0%) e a maioria dos doentes apresentava- se em estadios avançados da neoplasia (12/60% em estadios III ou IV). A falência da CPRE deveu-se à presença de obstrução no lúmen duodenal em 55.0% dos doentes (n = 11). Em todos os doentes foram utilizadas próteses metálicas totalmente cobertas, maioritariamente HotAxiosTM (n = 15; 75.0%). A taxa de sucesso técnico foi de 100% e de sucesso clínico foi de 89.5% ao 7.º dia (n = 17/19) e 93.3% ao 30.º dia (n = 14/15). Quatro doentes (20.0%) desenvolveram colangite nos primeiros 30 dias após o procedimento; não se verificaram complicações tardias e nenhum doente faleceu como complicação do procedimento. Em 2 doentes (10.0%) foi necessária reintervenção por migração da prótese, detetada incidentalmente. A sobrevida mediana foi de 93 dias (mínimo 5 - máximo 751). Conclusões: A CGE foi efetiva na descompressão biliar de obstruções malignas da via biliar distal, com elevado sucesso clínico e um perfil de segurança favorável.

Lane-Hamilton Syndrome in an Adult With Down Syndrome: A Case Report.

The Lane-Hamilton syndrome (LHS) is an extremely rare association between celiac disease (CD) and idiopathic pulmonary hemosiderosis (IPH), with only a few cases reported in the literature. The authors report a case of a 32-year-old man with Down syndrome who presented to the emergency department with a history of hemoptysis and chronic diarrhea. The complementary investigation revealed iron deficiency anemia and features suggestive of diffuse alveolar hemorrhage on computed tomography (CT) scan of the chest. After excluding all competing diagnosis, the IPH diagnosis was made. The biopsy of the small intestine confirmed CD and the diagnosis of LHS was established. A gluten-free diet and steroids were given to the patient with a very good clinical response. Since there is an established association between IPH and CD, if the diagnosis of IPH is made, it's recommended to screen for CD even in patients without gastrointestinal symptoms.

Immunogenicity and safety of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Taiwan.

BACKGROUND/PURPOSE: The immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae (H. Influenzae) protein D conjugate vaccine (PHiD-CV), co-administered with routine childhood vaccines, were assessed in Taiwanese infants. METHODS: In this open study, 230 healthy infants were primed with three doses of PHiD-CV (Synflorix) and diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine (DTPa-HBV-IPV/Hib vaccine) at 1.5, 3 and 6 months of age and two doses of oral human rotavirus vaccine at 1.5 and 3 months. Pneumococcal immune responses were assessed 1 month post-dose three, by 22F-inhibition ELISA and opsonophagocytic activity (OPA) assay. Local and general solicited/unsolicited symptoms and serious adverse events (SAEs) were recorded. RESULTS: At least 95.4% of participants had an antibody concentration ≥ 0.2 µg/mL against each vaccine serotype. At least 96.1% of participants had an OPA titer ≥ 8 against each vaccine serotype except 6B (87.3%). All infants, but one, were seropositive for antibodies against nontypeable H. influenzae protein D. Immune responses to the co-administered vaccines were good and in line with previous reports. PHiD-CV was well tolerated, with low (≤ 6.3%) incidences of grade 3 solicited local symptoms. The frequencies of general symptoms were in line with other pneumococcal conjugate vaccine studies. There were no systematic increases in incidences of solicited general or local symptoms with successive doses. There were no reports of grade 3 fever (rectal temperature > 40 °C) or SAEs considered to be causally related to vaccination. CONCLUSION: PHiD-CV co-administered with routine childhood vaccines within the first 6 months of life, was highly immunogenic, and well tolerated in Taiwanese infants.

Selection bias in patients proposed for neurosurgical versus endovascular treatment of aneurysms of the posterior communicating artery.

BACKGROUND: Microsurgical clipping and endovascular coiling are viable treatment options for posterior communicating artery (PComA) aneurysms, but there are still major limitations to evidence-based decisions regarding standard-of-care treatment. In this study, we aimed at assessing potential selection biases that may influence our ability to extract conclusions about the comparative effectiveness or efficacy of the aneurysm treatment. OBJECTIVE: To study the patient/aneurysm characteristics as possible biases in the option for endovascular or neurosurgical treatment of PComA aneurysms. METHODS: A single-center, retrospective cohort study was performed, including all patients with treated PComA aneurysms with neurosurgical clipping or endovascular coiling between January 2010 and January 2021. Clinical and morphological data were collected from electronic records, and statistical analysis was performed. RESULTS: A total of 64 patients was eligible for inclusion; 24 (37.5%) patients were proposed for neurosurgical treatment, while 40 (62.5%) for endovascular treatment; 10 patients (25%) crossed over to the clipping group whereas none crossed over to the coiling side. Actual treatment analysis showed significantly higher diameters of mother vessel (t-test, p = 0.034) and aneurysm neck (Mann-Whitney, p = 0.029) in the clipping group and higher aspect and dome-to-neck ratios in the endovascular group (Mann-Whitney, p = 0.008). A significantly higher vasospasm frequency was found in the clipping group but only in the intention-to-treat analysis (Chi-square, p = 0.032). CONCLUSION: Significant morphological differences between effective endovascular and surgical groups and differences in intention-to-treat analysis may limit the validity of a direct comparison between treatment options and suggest the presence of a possible selection bias.

Evaluation of the indirect impact of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine in a cluster-randomised trial.

BACKGROUND: In the nation-wide double-blind cluster-randomised Finnish Invasive Pneumococcal disease trial (FinIP, ClinicalTrials.gov NCT00861380, NCT00839254), we assessed the indirect impact of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against five pneumococcal disease syndromes. METHODS: Children 6 weeks to 18 months received PHiD-CV10 in 48 clusters or hepatitis B/A-vaccine as control in 24 clusters according to infant 3+1/2+1 or catch-up schedules in years 2009-2011. Outcome data were collected from national health registers and included laboratory-confirmed and clinically suspected invasive pneumococcal disease (IPD), hospital-diagnosed pneumonia, tympanostomy tube placements (TTP) and outpatient antimicrobial prescriptions. Incidence rates in the unvaccinated population in years 2010-2015 were compared between PHiD-CV10 and control clusters in age groups <5 and ≥5 years (5-7 years for TTP and outpatient antimicrobial prescriptions), and in infants <3 months. PHiD-CV10 was introduced into the Finnish National Vaccination Programme (PCV-NVP) for 3-month-old infants without catch-up in 9/2010. RESULTS: From 2/2009 to 10/2010, 45398 children were enrolled. Vaccination coverage varied from 29 to 61% in PHiD-CV10 clusters. We detected no clear differences in the incidence rates between the unvaccinated cohorts of the treatment arms, except in single years. For example, the rates of vaccine-type IPD, non-laboratory-confirmed IPD and empyema were lower in PHiD-CV10 clusters compared to control clusters in 2012, 2015 and 2011, respectively, in the age-group ≥5 years. CONCLUSIONS: This is the first report from a clinical trial evaluating the indirect impact of a PCV against clinical outcomes in an unvaccinated population. We did not observe consistent indirect effects in the PHiD-CV10 clusters compared to the control clusters. We consider that the sub-optimal trial vaccination coverage did not allow the development of detectable indirect effects and that the supervening PCV-NVP significantly diminished the differences in PHiD-CV10 vaccination coverage between the treatment arms.

Primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in infants in Mali and Nigeria: a randomized controlled trial.

BACKGROUND: Pneumonia is still the leading cause of death among children in Africa, and pneumococcal serotypes 1 and 5 are frequently isolated from African children with invasive pneumococcal disease below the age of 5 years. The immunogenicity, safety and reactogenicity of 3-dose primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were evaluated in infants in Mali and Nigeria. METHODS: In an open, randomized, controlled study, 357 infants received DTPw-HBV/Hib and OPV primary vaccination with (PHiD-CV group) or without (control group) PHiD-CV co-administration at 6, 10 and 14 weeks of age. Pneumococcal antibody responses and opsonophagocytic activity (OPA) were measured and adverse events (AEs) recorded. RESULTS: One month post-dose 3, ≥ 97.2% of PHiD-CV-vaccinated infants had an antibody concentration ≥ 0.2 µg/mL for each vaccine pneumococcal serotype except for 6B (82.0%) and 23F (87.6%) versus < 10% in the control group except for serotypes 14 (35.7%) and 19F (22.5%). For each vaccine serotype, ≥ 93.3% of PHiD-CV recipients had an OPA titre ≥ 8, except for serotypes 1 (87.6%) and 6B (85.4%), compared to < 10% in the control group, except for serotypes 7F (42.9%), 9V (24.1%) and 14 (24.5%). Anti-protein D geometric mean antibody concentrations were 3791.8 and 85.4 EL.U/mL in the PHiD-CV and control groups, respectively. Overall incidences of solicited and unsolicited AEs were similar between groups. CONCLUSIONS: In sub-Saharan African infants, PHiD-CV was immunogenic for all vaccine pneumococcal serotypes and protein D. Vaccine tolerability was generally comparable between the PHiD-CV and control groups. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00678301.

Immunogenicity, reactogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Mexican infants.

The immunogenicity and safety of the 10-valent pneumococcal conjugate vaccine, PHiD-CV, have been documented in European and Asian studies. In this open study conducted in Mexico (NCT00489554), 230 healthy infants received three doses of PHiD-CV and DTPa-HBV-IPV/Hib vaccines at 2, 4 and 6 months of age and two doses of oral human rotavirus vaccine at 2 and 4 months. Serotype-specific pneumococcal responses and opsonophagocytic activity (OPA) were measured one month post-dose 3. PHiD-CV's primary vaccination course was highly immunogenic against each of the 10 pneumococcal vaccine serotypes and carrier protein D. Antibody responses against pneumococcal serotypes and protein D were generally higher in Mexican infants compared with European antibody responses, and functional OPA responses were also higher or in the same range. The most frequent solicited local symptom was pain, with high but similar incidences of grade 3 pain reported at both injection sites (up to 15% of all doses). PHiD-CV was well tolerated, with no serious adverse events considered as causally related to vaccination. Most solicited symptoms were mild and there was no increase in incidence of solicited symptoms with successive vaccine doses.