Detailed Characteristics of Post-discharge Mortality in Acute Pancreatitis.

BACKGROUND & AIMS: The in-hospital survival of patients suffering from acute pancreatitis (AP) is 95% to 98%. However, there is growing evidence that patients discharged after AP may be at risk of serious morbidity and mortality. Here, we aimed to investigate the risk, causes, and predictors of the most severe consequence of the post-AP period: mortality. METHODS: A total of 2613 well-characterized patients from 25 centers were included and followed by the Hungarian Pancreatic Study Group between 2012 and 2021. A general and a hospital-based population was used as the control group. RESULTS: After an AP episode, patients have an approximately threefold higher incidence rate of mortality than the general population (0.0404 vs 0.0130 person-years). First-year mortality after discharge was almost double than in-hospital mortality (5.5% vs 3.5%), with 3.0% occurring in the first 90-day period. Age, comorbidities, and severity were the most significant independent risk factors for death following AP. Furthermore, multivariate analysis identified creatinine, glucose, and pleural fluid on admission as independent risk factors associated with post-discharge mortality. In the first 90-day period, cardiac failure and AP-related sepsis were among the main causes of death following discharge, and cancer-related cachexia and non-AP-related infection were the key causes in the later phase. CONCLUSION: Almost as many patients in our cohort died in the first 90-day period after discharge as during their hospital stay. Evaluation of cardiovascular status, follow-up of local complications, and cachexia-preventing oncological care should be an essential part of post-AP patient care. Future study protocols in AP must include at least a 90-day follow-up period after discharge.

Fluid resuscitation with balanced electrolyte solutions results in faster resolution of diabetic ketoacidosis than with 0.9% saline in adults - A systematic review and meta-analysis.

Fluid resuscitation during diabetic ketoacidosis (DKA) is most frequently performed with 0.9% saline despite its high chloride and sodium concentration. Balanced Electrolyte Solutions (BES) may prove a more physiological alternative, but convincing evidence is missing. We aimed to compare the efficacy of 0.9% saline to BES in DKA management. MEDLINE, Cochrane Library, and Embase databases were searched for relevant studies using predefined keywords (from inception to 27 November 2021). Relevant studies were those in which 0.9% saline (Saline-group) was compared to BES (BES-group) in adults admitted with DKA. Two reviewers independently extracted data and assessed the risk of bias. The primary outcome was time to DKA resolution (defined by each study individually), while the main secondary outcomes were changes in laboratory values, duration of insulin infusion, and mortality. We included seven randomized controlled trials and three observational studies with 1006 participants. The primary outcome was reported for 316 patients, and we found that BES resolves DKA faster than 0.9% saline with a mean difference (MD) of -5.36 [95% CI: -10.46, -0.26] hours. Post-resuscitation chloride (MD: -4.26 [-6.97, -1.54] mmoL/L) and sodium (MD: -1.38 [-2.14, -0.62] mmoL/L) levels were significantly lower. In contrast, levels of post-resuscitation bicarbonate (MD: 1.82 [0.75, 2.89] mmoL/L) were significantly elevated in the BES-group compared to the Saline-group. There was no statistically significant difference between the groups regarding the duration of parenteral insulin administration (MD: 0.16 [-3.03, 3.35] hours) or mortality (OR: -0.67 [0.12, 3.68]). Studies showed some concern or a high risk of bias, and the level of evidence for most outcomes was low. This meta-analysis indicates that the use of BES resolves DKA faster than 0.9% saline. Therefore, DKA guidelines should consider BES instead of 0.9% saline as the first choice during fluid resuscitation.

Cesarean delivery is associated with lower neonatal mortality among breech pregnancies - a systematic review and meta-analysis of preterm deliveries ≤32 weeks of gestation.

OBJECTIVE: To investigate the association between actual and planned modes of delivery, neonatal mortality, and short-term outcomes among preterm pregnancies ≤32 weeks of gestation. DATA SOURCES: A systematic literature search was conducted in three main databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 16, 2022. The protocol was registered in advance in the International Prospective Register of Systematic Reviews (CRD42022377870). STUDY ELIGIBILITY CRITERIA: Eligible studies examined pregnancies ≤ 32nd gestational week. All infants received active care, and the outcomes were reported separately by different modes of delivery. Singleton and twin pregnancies at vertex and breech presentations were included. Studies that included pregnancies complicated with preeclampsia and abruptio placentae were excluded. Primary outcomes were neonatal mortality and intraventricular hemorrhage. STUDY APPRAISAL AND SYNTHESIS METHODS: Articles were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random effects model-based odds ratios with corresponding 95% confidence intervals were calculated for dichotomous outcomes. ROBINS-I was used to assess the risk of bias. RESULTS: A total of nineteen observational studies were included involving a total of 16,042 preterm infants in this systematic review and meta-analysis. Actual cesarean delivery improves survival (odds ratio, 0.62; 95% confidence interval, 0.42 to 0.9) and decreases the incidence of intraventricular hemorrhage (odds ratio, 0.70; confidence interval, 0.57 to 0.85) compared to vaginal delivery. Planned cesarean delivery does not improve the survival of very and extremely preterm infants compared to vaginal delivery (odds ratio, 0.87; 95% confidence interval, 0.53 to 1.44). Subset analysis found significantly lower odds of death for singleton breech preterm deliveries born by both planned (odds ratio, 0.56; 95% confidence interval, 0.32 to 0.98) and actual (odds ratio, 0.34; 95% confidence interval, 0.13 to 0.88) cesarean delivery. CONCLUSION: Cesarean delivery should be the mode of delivery for preterm ≤32 weeks of gestation breech births due to the higher mortality in preterm infants born via vaginal delivery.

Acute Phase Protein Orosomucoid (Alpha-1-Acid Glycoprotein) Predicts Delayed Cerebral Ischemia and 3-Month Unfavorable Outcome after Aneurysmal Subarachnoid Hemorrhage.

The pathophysiology and consequences of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) remain incompletely understood. This study aims to investigate the role of orosomucoid (ORM) in aSAH, its potential as a marker for assessing the extent of EBI-induced damage, and its correlation with delayed cerebral ischemia (DCI) and functional recovery over a 3-month period. We collected serum specimens 72 h post-aSAH to measure ORM levels. The study included 151 aSAH patients and 105 healthy subjects. The serum ORM levels within the patient cohort significantly exceeded those in the control group (p < 0.001). The ORM value showed significant correlation with the admission WFNS (p < 0.0001) and mFS scores (p < 0.05). Substantially elevated serum ORM levels at 72 h post-aSAH were detected among patients experiencing DCI, as well as those with poor functional outcomes after 3 months (p = 0.009 and p < 0.001). Binary logistic regression analyses revealed that serum ORM at 72 h post-SAH was independently associated with DCI and 3-month functional outcome after adjusting for confounders. The early stage events of aSAH influence the level of ORM. ORM serves as a marker for assessing the extent of damage during EBI and is linked to the occurrence of DCI as well as unfavorable long-term functional outcomes.

Inflammatory bowel disease does not alter the clinical features and the management of acute pancreatitis: A prospective, multicentre, exact-matched cohort analysis.

OBJECTIVE AND AIMS: Acute pancreatitis in inflammatory bowel disease occurs mainly as an extraintestinal manifestation or a side effect of medications. We aimed to investigate the prognostic factors and severity indicators of acute pancreatitis and the treatment of patients with both diseases. DESIGN: We performed a matched case-control registry analysis of a multicentre, prospective, international acute pancreatitis registry. Patients with both diseases were matched to patients with acute pancreatitis only in a 1:3 ratio by age and gender. Subgroup analyses were also carried out based on disease type, activity, and treatment of inflammatory bowel disease. RESULTS: No difference in prognostic factors (laboratory parameters, bedside index of severity in acute pancreatitis, imaging results) and outcomes of acute pancreatitis (length of hospitalization, severity, and local or systemic complications) were detected between groups. Significantly lower analgesic use was observed in the inflammatory bowel disease population. Antibiotic use during acute pancreatitis was significantly more common in the immunosuppressed group than in the non-immunosuppressed group (p = 0.017). However, none of the prognostic parameters or the severity indicators showed a significant difference between any subgroup of patients with inflammatory bowel disease. CONCLUSION: No significant differences in the prognosis and severity of acute pancreatitis could be detected between patients with both diseases and with pancreatitis only. The need for different acute pancreatitis management is not justified in the coexistence of inflammatory bowel disease, and antibiotic overuse should be avoided.

The EFFect of dietary fat content on the recurrence of pancreaTitis (EFFORT): Protocol of a multicenter randomized controlled trial.

BACKGROUND: Around 20% of patients with acute pancreatitis (AP) will develop acute recurrent pancreatitis (ARP) and 10% will progress to chronic pancreatitis. While interventions to avoid recurrences exist for the two most common causes - abstinence for alcoholic and cholecystectomy for biliary pancreatitis - the are no known preventive measures in idiopathic ARP. Though it is not included in any of the guidelines, a low-fat diet is often recommended. Our aim is to test dietary fat reduction's effect on AP recurrence in a randomized controlled setting, in order to provide high-quality evidence for the validity of such an intervention. METHODS, DESIGN: Participants with at least 2 episodes of AP in the preceding 2 years of which the last episode was idiopathic will be randomized to one of two diets with different fat contents: a 'reduced fat diet' (15% fat, 65% carbohydrate, 20% protein) and a 'standard healthy diet' (30% fat, 50% carbohydrate, 20% protein; based on WHO recommendations). Participants will be followed-up for 2 years (visits will be scheduled for months 3, 6, 12, 18 and 24) during which they will receive a repeated session of nutritional guidance, complete food frequency questionnaires and data on relapse, mortality, BMI, cardiovascular parameters and serum lipid values will be collected. DISCUSSION: This study will determine the effect of modifying the dietary fat content on AP recurrence, mortality, serum lipids and weight loss in idiopathic cases.

Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients.

Pain, fatigue, and physical activity are major determinants of life quality in rheumatoid arthritis (RA). Janus kinase (JAK) inhibitors have emerged as effective medications in RA and have been reported to exert direct analgesic effect in addition to reducing joint inflammation. This analysis aims to give an extensive summary of JAK inhibitors especially focusing on pain and patient reported outcomes (PRO). MEDLINE, CENTRAL, Embase, Scopus, and Web of Science databases were searched on the 26 October 2020, and 50 randomized controlled trials including 24,135 adult patients with active RA met the inclusion criteria. JAK inhibitors yielded significantly better results in all 36 outcomes compared to placebo. JAK monotherapy proved to be more effective than methotrexate in 9 out of 11 efficacy outcomes. In comparison to biological disease-modifying antirheumatic drugs, JAK inhibitors show statistical superiority in 13 of the 19 efficacy outcomes. Analgesic effect determined using the visual analogue scale and American College of Rheumatology (ACR) 20/50/70 response rates was significantly greater in the JAK group in all comparisons, and no significant difference regarding safety could be explored. This meta-analysis gives a comprehensive overview of JAK inhibitors and provides evidence for their superiority in improving PROs and disease activity indices in RA.

Ultrafiltration is better than diuretic therapy for volume-overloaded acute heart failure patients: a meta-analysis.

Studies on the effectiveness of ultrafiltration (UF) in patients hospitalized with acute decompensated heart failure (ADHF) have led to heterogeneous study outcomes. This meta-analysis aimed to assess the impact of UF therapy in ADHF patients. We searched the medical literature to identify well-designed studies comparing UF with the usual diuretic therapy in this setting. Systematic evaluation of 8 randomized controlled trials enrolling 801 participants showed greater fluid removal (difference in means 1372.5 mL, 95% CI 849.6 to 1895.4 mL; p < 0.001), weight loss (difference in means 1.592 kg, 95% CI 1.039 to 2.144 kg; p < 0.001) and lower incidences of worsening heart failure (OR 0.63, 95% CI 0.43 to 0.94, p = 0.022) and rehospitalization for heart failure (OR 0.54, 95% CI 0.36 to 0.82, p = 0.003) without a difference in renal impairment (OR 1.386, 95% CI 0.870 to 2.209; p = 0.169) or all-cause mortality (OR 1.13, 95% CI 0.75 to 1.71, p = 0.546). UF increases fluid removal and weight loss and reduces rehospitalization and the risk of worsening heart failure in congestive patients, suggesting ultrafiltration as a safe and effective treatment option for volume-overloaded heart failure patients.

Evaluation of pulse wave velocity for predicting major adverse cardiovascular events in post-infarcted patients; comparison of oscillometric and MRI methods.

Increased aortic pulse wave velocity (PWV) has been proved as a strong predictor of major adverse cardiovascular events (MACE) in patients after myocardial infarction (MI). Due to the various technical approaches the level of high PWV values show significant differences. We evaluated the cut-off PWV values for MACE prediction using cardiac magnetic resonance imaging (CMR) and oscillometric methods for validating the prognostic value of high PWV in post-infarcted patients. Phase contrast imaging (PCI) and oscillometric based Arteriograph (AG) were compared in this 6 years follow-up study, including 75 consecutive patients of whom 49 suffered previous ST-elevation myocardial infarction (STEMI). Patients received follow-up for MACE comprising all-cause death, non-fatal MI, ischemic stroke, hospitalization for heart failure and coronary revascularization. An acceptable agreement and significant correlation (rho: 0.332, p < 0.01) was found between AG and CMR derived PWV values. The absolute values, however, were significantly higher for AG (median (IQR): 10.4 (9.2-11.9) vs 6.44 (5.64-7.5) m/s; p < 0.001). Totally 51 MACE events occurred during the 6 years follow-up period in post-infarcted patients. Kaplan-Meier analysis in both methods showed significantly lower event-free survival in case of high PWV (CMR: >6.47 m/s, AG: >9.625 m/s, p < 0.001, respectively). Multivariate Cox regression revealed PWV as a predictor of MACE (PWV CMR hazard ratio (HR): 1.31 (CI: 1.1-1.7), PWV AG HR: 1.24 (CI: 1.0-1.5), p < 0.05, respectively). Increased PWV derived by AG and CMR methods are feasible for MACE prediction in post-infarcted patients. However, adjusted cut-off values of PWV are recommended for different techniques to improve individual risk stratification.

Sensitivity to change of joint count composite indices in 72 patients with systemic sclerosis.

OBJECTIVES: We validated the responsiveness of joint count composite indices (JCCIs) in 72 patients with systemic sclerosis (SSc). METHODS: Changes in Disease Activity Score of 28 Joints using ESR and CRP (DAS28-ESR, DAS28-CRP), Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) were evaluated in a one-year follow-up study. Charts of patients including swollen/tender joint counts, laboratory signs of inflammation, and visual analogue scales referring to disease activity, severity and pain were also blindly categorized by two rheumatologists as improved, unchanged or deteriorated. These categories were used as references for the determination of effect size (ES) and standardised response mean (SRM). RESULTS: Articular inflammation improved in 15, deteriorated in 12, and remained unchanged in 45 (63%) patients with SSc based on the concordant opinion of two clinical investigators. All four JCCIs were sensitive to changes (ES>1; SRM>1). The correlation between changes in JCCIs and the physicians' evaluation was high (r >0.68; p<0.001). Arthritis was predominantly prone to change in patients with high JCCIs, impaired functional status, anti-RNA polymerase III antibodies and patients on DMARD therapy. Synovitis was more prevalent in patients with early diffuse SSc, and tended to improve during the follow-up. CONCLUSIONS: All four JCCIs were sensitive to changes, if tender/swollen joints were present at baseline. Articular inflammation was most prone to change in patients with high JCCIs, impaired functional status and already decreased health-related quality of life at baseline.

Heat therapy shows benefit in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

AIMS: Type-2 diabetes mellitus (T2DM) is a common health condition which prevalence increases with age. Besides lifestyle modifications, passive heating could be a promising intervention to improve glycemic control. This study aimed to assess the efficacy of passive heat therapy on glycemic and cardiovascular parameters, and body weight among patients with T2DM. METHODS: A systematic review and meta-analysis were reported according to PRISMA Statement. We conducted a systematic search in three databases (MEDLINE, Embase, CENTRAL) from inception to 19 August 2021. We included interventional studies reporting on T2DM patients treated with heat therapy. The main outcomes were the changes in pre-and post-treatment cardiometabolic parameters (fasting plasma glucose, glycated plasma hemoglobin, and triglyceride). For these continuous variables, weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Study protocol number: CRD42020221500. RESULTS: Five studies were included in the qualitative and quantitative synthesis, respectively. The results showed a not significant difference in the hemoglobin A1c [WMD -0.549%, 95% CI (-1.262, 0.164), p = 0.131], fasting glucose [WMD -0.290 mmol/l, 95% CI (-0.903, 0.324), p = 0.355]. Triglyceride [WMD 0.035 mmol/l, 95% CI (-0.130, 0.200), p = 0.677] levels were comparable regarding the pre-, and post intervention values. CONCLUSION: Passive heating can be beneficial for patients with T2DM since the slight improvement in certain cardiometabolic parameters support that. However, further randomized controlled trials with longer intervention and follow-up periods are needed to confirm the beneficial effect of passive heat therapy.

Screening for the presence of scleroedema adultorum of Buschke in patients with diabetes mellitus: newly diagnosed patients had a high prevalence of dyslipidaemia.

BACKGROUND: Scleroedema adultorum of Buschke is a rare disorder characterized by fibromucinous thickening of the dermis that manifests mainly at the nape of the neck and on the upper back and shoulders. This study screened patients with diabetes mellitus for skin hardening caused by scleroedema adultorum of Buschke and characterized the clinical and laboratory findings in patients with newly identified cases, with a focus on lipid metabolism abnormalities and vascular complications. METHODS: Out of 113 consecutive patients with diabetes, 11 (9.7%) new scleroedema patients, all with type 2 diabetes, were found. Their clinical and laboratory data were compared to those of the rest of the screened patients and to those of a cohort of 15 patients with scleroedema and diabetes who were already being treated in a tertiary clinical centre at the University of Pécs. RESULTS: Higher proportions of patients with dyslipidaemia, hypertriglyceridemia (P < 0.05) and increased mean levels of non-high-density lipoprotein cholesterol (non-HDL-C) were found (P < 0.01) in both scleroedema groups than in the group without scleroedema. Stroke and venous thromboembolism (VTE) were more frequently found in the histories of both the newly identified scleroedema group (each 3/11; 27.3%) and the treated cohort (each 6/15; 40.0%) than in the group without scleroedema (6/102; 5.9% in cases of stroke P = 0.021, P < 0.001; and 14/102; 13.7%; P < 0.05 in cases of VTE, respectively). Based on binary logistic regression, a high non-HDL-C level (odds ratio (OD): 3.338, confidence interval (CI): 1.77-6.28; P < 0.001) and insulin treatment (OR 7.64, CI 1.9-29.3; P = 0.003) were independent predictors of scleroedema in patients with diabetes mellitus. CONCLUSIONS: Diabetes patients with scleroedema had more severe dyslipidaemia and higher occurrence of vascular complications compared to those without scleroedema. In addition to poorly controlled type 2 diabetes mellitus requiring insulin treatment, high non-HDL-C levels may be another contributing factor to the development of scleroedema. TRIAL REGISTRATION: NCT04335396 .

Development of disturbance of consciousness is associated with increased severity in acute pancreatitis.

BACKGROUND: Disturbance of consciousness (DOC) may develop in acute pancreatitis (AP). In clinical practice, it is known that DOC may worsen the patient's condition, but we have no exact data on how DOC affects the outcome of AP. METHODS: From the Hungarian Pancreatic Study Groups' AP registry, 1220 prospectively collected cases were analyzed, which contained exact data on DOC, included patients with confusion, delirium, convulsion, and alcohol withdrawal, answering a post hoc defined research question. Patients were separated to Non-DOC and DOC, whereas DOC was further divided into non-alcohol related DOC (Non-ALC DOC) and ALC DOC groups. For statistical analysis, independent sample t-test, Mann-Whitney, Chi-squared, or Fisher exact test were used. RESULTS: From the 1220 patients, 47 (3.9%) developed DOC, 23 (48.9%) cases were ALC DOC vs. 24 (51.1%) Non-ALC DOC. Analysis between the DOC and Non-DOC groups showed a higher incidence of severe AP (19.2% vs. 5.3%, p < 0.001), higher mortality (14.9% vs. 1.7%, p < 0.001), and a longer length of hospitalization (LOH) (Me = 11; IQR: 8-17 days vs. Me = 9; IQR: 6-13 days, p = 0.049) respectively. Patients with ALC DOC developed more frequently moderate AP vs. Non-ALC DOC (43.5% vs. 12.5%), while the incidence of severe AP was higher in Non-ALC vs. ALC DOC group (33.3% vs. 4.4%) (p < 0.001). LOH showed a tendency to be longer in Non-ALC DOC compared to ALC DOC, respectively (Me:13; IQR:7-20 days vs. Me:9.5; IQR:8-15.5 days, p = 0.119). CONCLUSION: DOC during AP is associated with a higher rate of moderate and severe AP and increases the risk of mortality.

Hypertriglyceridemia-induced acute pancreatitis: A prospective, multicenter, international cohort analysis of 716 acute pancreatitis cases.

BACKGROUND: Hypertriglyceridemia is the third most common cause of acute pancreatitis (AP). It has been shown that hypertriglyceridemia aggravates the severity and related complications of AP; however, detailed analyses of large cohorts are contradictory. Our aim was to investigate the dose-dependent effect of hypertriglyceridemia on AP. METHODS: AP patients over 18 years old who underwent triglyceride measurement within the initial three days were included into our cohort analysis from a prospective international, multicenter AP registry operated by the Hungarian Pancreatic Study Group. Data on 716 AP cases were analyzed. Six groups were created based on the highest triglyceride level (<1.7 mmol/l, 1.7-2.19 mmol/l, 2.2-5.59 mmol/l, 5.6-11.29 mmol/l, 11.3-22.59 mmol/l, ≥22.6 mmol/l). RESULTS: Hypertriglyceridemia (≥1.7 mmol/l) presented in 30.6% of the patients and was significantly and dose-dependently associated with younger age and male gender. In 7.7% of AP cases, hypertriglyceridemia was considered as a causative etiological factor (≥11.3 mmol/l); however, 43.6% of these cases were associated with other etiologies (alcohol and biliary). Hypertriglyceridemia was significantly and dose-dependently related to obesity and diabetes. The rates of local complications and organ failure and maximum CRP level were significantly and dose-dependently raised by hypertriglyceridemia. Triglyceride above 11.3 mmol/l was linked to a significantly higher incidence of moderately severe AP and longer hospital stay, whereas triglyceride over 22.6 mmol/l was significantly associated with severe AP as well. CONCLUSION: Hypertriglyceridemia dose-dependently aggravates the severity and related complications of AP. Diagnostic workup for hypertriglyceridemia requires better awareness regardless of the etiology of AP.

Does Co-occurred Cerebral Palsy Change the Prognosis of West Syndrome?

AIM: We aimed to examine the occurrence of cerebral palsy (CP) in children with West syndrome (WS), to estimate the possible causative factors by analyzing the neuroimaging examinations of patients, to evaluate their cognitive/motor function and epileptic status and to compare the prognosis of children with double pathology of WS and CP and of those without CP. METHODS: The clinical and magnetic resonance imaging (MRI) data of 62 patients with West syndrome were evaluated. A total of 39 of 62 patients (63%) suffered from CP (CP group). The non-CP group included 23 patients. RESULTS: Abnormal MRI was found in 55/62 (89%) patients. Main anomalies were: brain malformation (21), hypoxic-ischemic encephalopathy (13), cerebrovascular insult (8), infection (7), and other anomalies (6). In the CP group, the most common MRI abnormalities included pre/perinatal hypoxia/ischemia, brain malformation, cerebrovascular insult, and infection. In the non-CP group, brain malformations were the most frequent. Significantly more negative MRIs were found in the non-CP group. More than 60% of the patients were severely cognitively impaired, almost 90% of them had CP. Not only the occurrence of intellectual disability was lower in the non-CP group, but its severity was milder as well. A total of 78% of the children with CP had a very severe motor disability. Fifty-four percent in the CP and 67% in the non-CP group had therapy-resistant epilepsy. CONCLUSION: WS has an especially unfavorable prognosis: cerebral anomaly was confirmed in 89% of our patients. CP was present in almost two-thirds of the children with WS, most of them had severe cognitive and motor deficits.

The quadrivalent HPV vaccine is protective against genital warts: a meta-analysis.

BACKGROUND: The quadrivalent human papillomavirus (HPV) vaccine has been assumed to give protection against genital warts (GW) as well as cervical cancer. Our main question was whether HPV vaccine has any effects on the prevention of GW reported in randomised controlled clinical trials (RCTs) and time-trend analyses. METHODS: This meta-analysis was performed according to the PRISMA guidelines using the PICO format. We searched in three electronic databases (PubMed, Embase, Cochrane Trials), and assessed heterogeneity using the Q-test and I-squared statistics, meta-regression was also performed. Odds ratios (OR) and their confidence intervals (CI) were calculated. The sensitivity was tested by leave-one-out method. We evaluated the presence of publication bias using the funnel plot graph and the Copas selection model. The strength of evidence was assessed using the GRADE approach. RESULTS: Eight RCTs (per-protocol populations) and eight time-trend ecological studies were included in this meta-analysis. A significant reduction (pooled OR = 0.03, 95% CI: 0.01-0.09; I-squared = 53.6%) of GW in young women was recorded in RCTs, and in time-trend analyses both in young women (pooled OR = 0.36, CI 95% = 0.26-0.51; I-squared = 98.2%), and in young men (pooled OR = 0.69, 95% CI = 0.61-0.78; I-squared = 92.7%). In subgroup analysis, a significant reduction of the number of GW events was observed especially in women under 21 years (pooled OR = 0.33, 95% CI = 0.17-0.63). Leave-one-out analysis showed that similar results could be obtained after excluding one study, meta-regression did not show significant difference. CONCLUSIONS: Prophylactic, quadrivalent HPV vaccination can prevent GW in healthy women and men, therefore, it should be included in routine immunization programme.

The usefulness of MRI Classification System (MRICS) in a cerebral palsy cohort.

AIM: Our aim was to investigate perinatal and clinical factors associated with children with cerebral palsy (CP) using magnetic resonance imaging (MRI). The distribution of MRI patterns was based on the MRI classification system (MRICS). Associations between perinatal/clinical characteristics and MRI patterns were also investigated. METHODS: A population-based cohort study was performed; those 257 children (58.0% male) were enrolled from our CP database who born between 1990 and 2015 in Southwest Hungary and had at least one MRI scan. RESULTS: Brain maldevelopments were found in 18.7% of our patients, 83.7% of those born at term. Grey matter lesions were found in 19.8% of our patients, and 80.0% of those children were born at term. The rate of white matter injuries was the highest (35.4%); 69.0% of these patients were born before 37th week of gestation. MRI revealed no abnormalities in 13.6% of children with CP. The best values of gross/fine motor and cognitive function tests were found in children with normal MRI and with grey matter injuries. The prevalence of epilepsy was above 60% in every group with an abnormal MRI. CONCLUSION: MRI results were conclusive in 86.4% of children with CP. It is highly encouraged to perform cranial MRI in every patient with CP.

Mechanical stress alters protein O-GlcNAc in human periodontal ligament cells.

Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors. However, O-GlcNAc's response to mechanical stress has not been investigated yet. As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells. In this study, PDL cells isolated from premolars extracted for orthodontic indications were exposed to 0, 1.5, 3, 7 and 14 g/cm2 compression forces for 12 hours. Cell viability was measured by flow cytometry, and protein O-GlcNAc was analysed by Western blot. Cellular structure and intracellular distribution of O-GlcNAc was studied by immunofluorescence microscopy. We found that between 1.5 and 3 g/cm2 mechanical compression, O-GlcNAc significantly elevated; however, at higher forces O-GlcNAc level was not increased. We also found that intracellular localization of O-GlcNAc proteins became more centralized under 2 g/cm2 compression force. Our results suggest that structural changes stimulated by compression forces have a significant effect on the regulation of O-GlcNAc; thus, it might play a role in the mechanical stress adaptation of PDL cells.

Follicular fluid progesterone concentration is associated with fertilization outcome after IVF: a systematic review and meta-analysis.

Follicular fluid is a key biochemical environment for oocyte development. The potential effect of follicular progesterone level on successful fertilization is a subject of debate, and so the aim of this study was to provide a summary of the currently available evidence on the association between follicular fluid progesterone level and fertilization outcome. To do so, a systematic review and a meta-analysis were performed, with the literature searches being conducted in three databases (PubMed, Embase and the Cochrane Library) to identify all relevant studies published up to 19 August 2017. Data were available from 13 studies (four intracytoplasmic sperm injection [ICSI] and nine conventional IVF) and 1009 individually aspirated follicular fluid samples were included in the analysis. The progesterone levels in follicular fluid were significantly higher in normal fertilization than in failed fertilization, both in conventional IVF (33% difference, P < 0.001) and ICSI (34% difference, P = 0.004). Although these data show that fertilized oocytes are derived from follicles with higher levels of progesterone, the results must be interpreted with caution, because of various progesterone measurement methods and different treatment protocols and it is too early to state that follicular fluid progesterone level could be considered as a marker for oocyte quality.

Transpancreatic Sphincterotomy Is Effective and Safe in Expert Hands on the Short Term.

In cases of difficult biliary cannulation, transpancreatic sphincterotomy (TPS) can be an alternative approach of biliary access. However, its success and safety profile have not been studied in detail. A systematic review and meta-analysis were performed to study the overall cannulation success and adverse events of TPS. These outcomes were also compared to other advanced cannulation methods. A systematic literature search was conducted to find all relevant articles containing data on TPS. Successful biliary cannulation and complications rates [post-ERCP pancreatitis (PEP), bleeding, and perforation rates] were compared in the pooled analyses of prospective comparative studies. The overall outcomes were calculated involving all studies on TPS. TPS was superior compared to needle-knife precut papillotomy (NKPP) and the double-guidewire method (DGW) regarding cannulation success (odds ratio [OR] 2.32; 95% confidence interval [CI] 1.37-3.93; and OR 2.72; 95% CI 1.30-5.69, respectively). The rate of PEP did not differ between TPS and NKPP or DGW; however, TPS (only retrospective studies were available for comparison) proved to be worse than needle-knife fistulotomy in this regard (OR 4.62; 95% CI 1.36-15.72). Bleeding and perforation rates were similar among these advanced techniques. There were no data about long-term consequences of TPS. The biliary cannulation rate of TPS is higher than that of the other advanced cannulation techniques, while the safety profile is similar to those. However, no long-term follow-up studies are available on the later consequences of TPS; therefore, such studies are strongly needed for its full evaluation.