Comparative maintenance performance of all biologic agents and small molecules in ulcerative colitis: a network meta-analysis.

BACKGROUND AND AIMS: Βiologic agents and small molecules have expanded the therapeutic armamentarium of moderate to severe ulcerative colitis (UC). However, their comparative efficacy and safety performance as maintenance treatments have not been sufficiently explored. We performed a systematic review and network meta-analysis (NWM) to assess the comparative efficacy and safety of all approved and emerging treatments for maintenance in moderate to severe UC. METHODS: We searched Pubmed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through April 2023. The primary endpoint was clinical remission at the end of the maintenance therapy. Data were analyzed by means of a Bayesian NWM. The ranking probability concerning efficacy and safety was evaluated by means of surfaces under cumulative ranking (SUCRA) values. RESULTS: There were 20 eligible RCTs with 7660 patients randomized to 20 treatments. RCTs were grouped into two study designs, that is, re-randomization of patients after an induction period and treat-through patients. Concerning efficacy, in re-randomized patients, upadacitinib 30 mg/day was ranked first (SUCRA 94.9%) whereas in treat-through patients etrasimod 2 mg/day was ranked first (SUCRA 91.1%). The integrated efficacy-safety hierarchical analysis, showed that tofacitinib 10 mg had the best efficacy-safety therapeutic profile in re-randomized patients, whereas in treat-through patients infliximab 3.5 mg/Kg Q8W showed the best efficacy-safety profile. CONCLUSION: For maintenance treatment, in moderate to severe UC, this NWM showed that upadacitinib 30 mg/day and etrasimod 2 mg/day were ranked best for efficacy in re-randomized and treat-through patients respectively. Tofacitinib 10 mg/day and infliximab 3.5 mg/Kg Q8W showed the best efficacy-safety therapeutic profile in re-randomized and treat-through patients respectively.

H. Pylori Treatment in the COVID-19 Era. What Have We Learned So Far?

PURPOSE OF REVIEW: CoronaVirus Disease of 2019 (COVID-19) has negatively influenced the management of multiple conditions in regards to the gastroenterology patient. An equivalent change in the management of Helicobacter pylori (H. pylori)-related diseases was reported, as practically no eradication treatment was offered during most of the pandemic. Given the scarcity of published data, we performed a literature review trying to elucidate the effect of COVID-19 on H. pylori treatment. RECENT FINDINGS: COVID-19 has produced more questions than answers as to the outcome of COVID-19 in H. Pylori infected patients, post-COVID-19 patients treated for H. pylori, acid suppression and COVID-19 incidence and outcomes, and H. pylori eradication treatment in patients having recovered from COVID-19. We strongly believe that this scientific uncertainty produced by the COVID-19 pandemic has set up the stage for an incremental change in H. pylori treatment as COVID-19 has offered us the chance to speed up how we will, in the near future, approach patients with a possible Η. pylori infection.

The Effect of Oral Iron Supplementation/Fortification on the Gut Microbiota in Infancy: A Systematic Review and Meta-Analysis.

(1) Background: Iron is an essential metal for the proper growth and neurodevelopment of infants. To prevent and treat iron deficiency, iron supplementation or fortification is often required. It has been shown, though, that it affects the synthesis of gut microbiota. (2) Methods: This paper is a systematic review and meta-analysis of the effect of oral iron supplementation/fortification on the gut microbiota in infancy. Studies in healthy neonates and infants who received per os iron with existing data on gut microbiota were included. Three databases were searched: PUBMED, Scopus, and Google Scholar. Randomized controlled trials (RCTs) were included. Quality appraisal was assessed using the ROB2Tool. (3) Results: A total of six RCTs met inclusion criteria for a systematic review, and four of them were included in the meta-analysis using both the fixed and random effects methods. Our results showed that there is very good heterogeneity in the iron group (I2 = 62%), and excellent heterogeneity in the non-iron group (I2 = 98%). According to the meta-analysis outcomes, there is a 10.3% (95% CI: -15.0--5.55%) reduction in the bifidobacteria population in the iron group and a -2.96% reduction for the non-iron group. There is a confirmed difference (p = 0.02) in the aggregated outcomes between iron and non-iron supplement, indicative that the bifidobacteria population is reduced when iron supplementation is given (total reduction 6.37%, 95%CI: 10.16-25.8%). (4) Conclusions: The abundance of bifidobacteria decreases when iron supplementation or fortification is given to infants.

Advances in the pharmacological and regulatory management of multidrug resistant Helicobacter pylori.

INTRODUCTION: Antibiotic resistance of Helicobacter pylori (H. pylori) hampers the success of eradication and in recent years multidrug resistance (MDR) shows an increase worldwide. AREAS COVERED: This review covers current aspects of pharmacological and regulatory management of MDR-resistant H. pylori infection. EXPERT OPINION: MDR H. pylori is increasing worldwide and its prevalence varies both between continents and countries. High consumption and misuse of antibiotics, H. pylori treatment failures and bacterial factors such as mutations, efflux pumps and biofilms are among the factors associated with MDR. Important steps for confronting the rise of MDR H. pylori strains should follow the principles of antibiotic stewardship, i.e. eradication regimens should be optimized with regard to all aspects of therapy, including drugs, doses, formulation, frequency of administration, administration in relation to meals and duration of therapy that reliably achieve at least 90% (preferably >95%) cure rates in adherent patients with susceptible infections.

The Effects of Dexmedetomidine on Children Undergoing Magnetic Resonance Imaging: A Systematic Review and Meta-Analysis.

BACKGROUND: Magnetic Resonance Imaging (MRI) is a valuable diagnostic tool but often requires sedation to complete, especially in children. Dexmedetomidine (DEX) is an a2 agonist, for which there are experimental findings that support its potential neuroprotective effects. Given the potential risks of anesthetic drugs, we ran this study to examine DEX's effectiveness and cardiopulmonary safety as a sedative drug for children undergoing MRI. MATERIAL AND METHODS: Systematic research was conducted in PubMed, Google Scholar, Scopus and Cochrane databases for randomized controlled trials published between 2010 and 6th/2022 and involving children undergoing MRI who received DEX as sedative medication. The records which met the including criteria, after indexing via the PRISMA chart and assessing for bias, were processed, and a meta-analysis was carried out with the random effects method. RESULTS: Thirteen studies were included. Out of 6204 measurements obtained, in 4626, it was planned for the participants to only receive DEX (measure group) as an anesthetic drug throughout the procedure. The participants' mean age was 57 months (Ι2 = 4%, τ2 = 0.5317, p = 0.40). A total of 5.6% (95% CI: 0.6-14.1%, I2 = 98%, p < 0.01) of the patients needed a second dose of DEX. In total, 6% (95% CI: 1-15%, I2 = 93%, τ2 = 0.0454, p < 0.01) required the administration of another drug, besides DEX, to complete the imaging (sedation failure). The effectiveness of the only-DEX method was 99% (95% CI: 97.5-100%, I2 = 81%, τ2 = 0.0107, p < 0.01). The whole rate of adverse events was 15% (95% CI: 9.3-21.5%, I2 = 92%, p < 0.01). Hypotension was reported in 8.7% of the cases (95% CI: 3.1-16.4%, I2 = 84%, p < 0.01), hypertension in 1.1% (95% CI: 0-5.4%, I2 = 89%, p < 0.01), bradycardia in 10% (95% CI: 4-18%, I2 = 95%, p < 0.01) and desaturation in 1.2% (95% CI: 0-4%, I2 = 68%, p < 0.01). There was no statistically significant incidence in respiratory rate decrease (comparing the children who received DEX to their baseline). Five cases of vomiting and one of apnea were recorded. CONCLUSIONS: Given that DEX seems to be an effective as well as respiratory and hemodynamically safe drug, it may be a future spotlight in (pediatric) sedation for imaging procedures such as MRI.

Current role of narrow band imaging in diagnosing gastric intestinal metaplasia: a systematic review and meta-analysis of its diagnostic accuracy.

Background: Gastric intestinal metaplasia (GIM) can be missed by random gastric biopsies taken during white light endoscopy. Narrow band imaging (NBI) may potentially improve the detection of GIM. However, pooled estimates from prospective studies are lacking and the diagnostic accuracy of NBI in detecting GIM needs to be more precisely defined. The aim of this systematic review and meta-analysis was to study the diagnostic performance of NBI in detecting GIM. Methods: PubMed/Medline and EMBASE were screened for studies examining GIM in relation to NBI. Data from each study were extracted and calculations of pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratios (DORs), and areas under the curve (AUCs) were performed. Fixed or random effects models, were used as appropriate, depending on the presence of significant heterogeneity. Results: We included 11 eligible studies in the meta-analysis, comprising 1672 patients. NBI showed a pooled sensitivity of 80% (95% confidence interval [CI] 69-87), specificity of 93% (95%CI 85-97), DOR 48 (95%CI 20-121), and AUC of 0.93 (95%CI 0.91-0.95) in detecting GIM. Conclusions: This meta-analysis showed that NBI is a reliable endoscopic means of detecting GIM. NBI with magnification performed better than NBI without magnification. However, better designed prospective studies are needed to precisely determine the diagnostic role of NBI, especially in high-risk populations where early detection of GIM can impact gastric cancer prevention and survival.

Non-Typical Clinical Presentation of COVID-19 Patients in Association with Disease Severity and Length of Hospital Stay.

BACKGROUND: This study aimed to investigate the incidence of non-typical symptoms in ambulatory patients with mild-to-moderate COVID-19 infection and their potential association with disease progression. MATERIALS AND METHODS: Data on the symptomatology of COVID-19 patients presenting to the fast-track emergency department were collected between March 2020 and March 2021. Fever, cough, shortness of breath, and fatigue-weakness were defined as "typical" symptoms, whereas all other symptoms such as nasal congestion, rhinorrhea, gastrointestinal symptoms, etc., were defined as "non-typical". RESULTS: A total of 570 COVID-19 patients with a mean age of 42.25 years were included, the majority of whom were male (61.3%; N = 349), and were divided according to their symptoms into two groups. The mean length of hospital stay was found to be 9.5 days. A higher proportion of patients without non-typical symptoms were admitted to the hospital (p = 0.001) and the ICU (p = 0.048) as well. No significant differences were observed between non-typical symptoms and outcome (p = 0.685). Patients who did not demonstrate at least one non-typical symptom had an extended length of stay (p = 0.041). No statistically significant differences in length of hospital stay were associated with individual symptoms. CONCLUSION: With the possible exception of gastrointestinal symptoms, non-typical symptoms of COVID-19 at baseline appear to predispose to a milder disease.

Comparative Efficacy and Tolerability of Janus Kinase Inhibitor Therapies for Moderate to Severe Crohn's Disease: Α Network Meta-analysis.

BACKGROUND AND AIMS: A number of Janus kinase (JAK) inhibitors (tofacitinib, filgotinib, upadacitinib) have been tested for moderate and severe Crohn's disease (CD) in randomized control trials (RCTs). However, data on their comparative efficacy and tolerability is lacking. We aimed to study their performance comparatively, by means of network meta-analysis (NWM). METHODS: We searched the Pubmed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through March 2021 and data was extracted. A bayesian NWM was performed to investigate the efficacy and tolerability of the above JAK inhibitors and to explore their rank order in treating moderate and severe CD patients. The cumulative ranking probability for each intervention at the end of treatment period, was evaluated by means of surfaces under cumulative ranking (SUCRA) values. RESULTS: Four RCTs were entered into this NWM. They included 811 patients totally, randomized to 11 interventions, i.e. placebo, tofacitinib (1mg BID, 5mg BID, 10mg BID, 15mg BID), filgotinib 200 OD and upadacitinib (3 mg BID, 6 mg BID, 12 mg BID, 24 mg BID and 24mg OD). Two upadacitinib doses (6 mg BID and 24 mg BID) and filgotinib 200 OD, performed best as judged by the relevant forest plots, league matrixes, rankograms, SUCRA values (96.7%, 84,6 %and 78,7%, respectively) and the clustered ranking plots for efficacy and tolerability. CONCLUSIONS: Upadacitinib 6 mg BID, upadacitinib 24 mg BID and filgotinib 200 OD performed better as induction therapies in comparison to control therapies. Consequently, these regimens may play a therapeutic role in CD and therefore they merit further evaluation with well-designed RCTs.

Comparative effectiveness of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: a network meta-analysis of randomized controlled studies.

BACKGROUND: There is evidence demonstrating the beneficial effects of 5-hydroxytryptamine 3 receptor antagonists (5-HT3) for the treatment of non-constipated irritable bowel syndrome (NC-IBS). We aimed to determine the comparative effectiveness of 5-HT3 antagonists in NC-IBS, as evidenced by the results of a network meta-analysis (NWM) of published relevant randomized controlled trials (RCTs). METHODS: We searched the PubMed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through September 2020 and data from each selected RCT were extracted. A Bayesian NWM was then performed to investigate the efficacy of 5-HT3 antagonists and to explore the effectiveness rank order in treating NC-IBS patients. RESULTS: Twenty-one eligible RCTs were identified and entered into this NWM. They included a total of 10,421 NC-IBS patients, randomized to alosetron, cilansetron, ondansetron, ramosetron, placebo, and mebeverine. The cumulative ranking probability for each intervention at the end of treatment period, was evaluated by means of surfaces under cumulative ranking (SUCRA) values. These results showed that alosetron had the best performance for global symptom improvement (SUCRA 0.82), cilansetron showed the best performance (SUCRA 0.90) for abdominal pain/discomfort improvement, while ondansetron (SUCRA 0.98) was by far the best choice concerning bowel habits/consistency improvement. The control regimens (mebeverine and placebo) represented the least efficacious interventions. CONCLUSIONS: This NWM showed that 5-HT3 receptor antagonists performed better in comparison to control drugs. Consequently, this class of drugs may play an important role in improving the debilitating symptoms in NC-IBS patients, in particular those with diarrhea.

When in Trouble Think of the Bubble: Paradoxical Cerebral Arterial Gas Embolism after Endoscopic Retrograde Cholangiopancreatography.

Air embolism (a result of direct communication with the vasculature and an external pressure gradient from the gastrointestinal or the biliary tract), although rare, is a potentially devastating adverse event seen in endoscopic retrograde cholangiopancreatography (ERCP) procedures. Whether venous, arterial, or paradoxical, the clinical presentation ranges from asymptomatic patients to cardiorespiratory arrest. This is of particular importance because it makes the diagnosis of air embolism even more difficult in an already sedated patient. Since early recognition increases the chances of patients' survival, endoscopists should be highly motivated and trained to recognize this complication as early as possible. With only 60 cases of air embolism reported (and even fewer related to paradoxical air embolism), we aimed to report a case of paradoxical cerebral air embolism in a patient undergoing ERCP due to a common bile duct stricture and to provide a mini-review of this clinical entity that can serve as a bedside quick reference guide for endoscopists worldwide.

Gastrointestinal involvement in COVID-19 patients: a retrospective study from a Greek COVID-19 referral hospital.

BACKGROUND: Much attention has been paid to the study and reporting of gastrointestinal (GI) symptoms in COVID-19 patients. Moreover, an increasing number of COVID-19 patients have been noted to experience hepatic and pancreatic injury. In this study, we retrospectively investigated symptoms and laboratory findings related to the GI system in a single center in Athens, Greece, and assessed the role of these parameters in relation to survival and disease severity. METHOD: We retrospectively studied 61 adult COVID-19 patients admitted to the Army Share Fund Hospital (NIMTS) in Athens, Greece, from April 6th to May 6th, 2020. RESULTS: Sixty-one COVID-19 cases were assessed in the study period. Regarding both survival and disease severity, diarrhea was the most common finding. The multivariate analysis revealed that elevated serum aspartate aminotransferase levels and low serum albumin levels were associated with worse patient survival (odds ratio [OR] 1.029, 95% confidence interval [CI] 1.007-1.05, P=0.0088; and OR 0.219, 95%CI 0.066-0.723, P=0.0127, respectively). As far as disease severity is concerned, only a low serum albumin level (measured at hospital admission) was correlated with more severe disease (OR 0.025, 95%CI 0.004-0.161, P=0.0001). CONCLUSIONS: Outpatients with new-onset GI symptoms should be considered for COVID-19 testing in a high COVID-19 prevalence setting, as these symptoms are observed more and more in clinical settings. As prospective studies begin to emerge, clinicians will have more robust research data to diagnose COVID-19 patients earlier and identify patients in need of more intensive treatment.

Gastric ischemic preconditioning may reduce the incidence and severity of anastomotic leakage after οesophagectomy: a systematic review and meta-analysis.

Anastomotic leakage after esophagectomy is a severe and life-threatening complication. Gastric ischemic preconditioning is a strategy for the improvement of anastomotic healing. Aim of this systematic review and meta-analysis is to investigate the impact of gastric ischemic preconditioning on postoperative morbidity. A systematic literature search was performed to identify studies comparing patients undergoing gastric ischemic preconditioning before esophagectomy with nonpreconditioned patients. Meta-analysis was conducted for the overall incidence of anastomotic leakage, severe anastomotic leakage, anastomotic stricture, postoperative morbidity, and mortality. Mantel-Haenszel odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed concerning preconditioning technique, the interval between preconditioning and surgery and the extent of preconditioning. Fifteen cohort studies were identified. Gastric preconditioning was associated with reduced overall incidence of anastomotic leakage (OR 0.73; 95% CI, 0.53-1.0; P = 0.050) and severe anastomotic leakage (OR 0.27; 95% CI, 0.14-0.50; P < 0.010), but not with anastomotic stricture (OR 1.18; 95% CI 0.38 to 3.66; P = 0.780), major postoperative morbidity (OR 1.03; 95% CI 0.45 to 2.36; P = 0.940) or mortality (OR 0.69; 95% CI 0.39 to 1,23; P = 0.210). Subgroup analyses did not identify any differences between embolization and ligation while increasing the interval between preconditioning and esophagectomy as well as the extent of preconditioning might be beneficial. Gastric ischemic preconditioning may be associated with a reduced incidence of overall and severe anastomotic leakage. Randomized studies are necessary to further evaluate its impact on leakage, refine the technique and define patient populations that will benefit the most.

10-Day Versus 14-Day Quadruple Concomitant Nonbismuth Therapy for the Treatment of Helicobacter pylori Infection: Results From a Randomized Prospective Study in a High Clarithromycin Resistance Country.

GOALS: The aim of this study was to investigate the implementation of a 14-day quadruple nonbismuth concomitant regimen, as proposed by recent Guidelines and Consensus Statements. BACKGROUND: In Greece, a region with >20% clarithromycin resistance where bismuth is unavailable, the 10-day quadruple concomitant scheme has already been adopted as the accepted first-line Helicobacter pylori eradication treatment. STUDY: Our prospective randomized study included 364 patients with newly diagnosed H. pylori infection, randomized to receive a 10-day or a 14-day nonbismuth quadruple concomitant scheme. Treatment outcome was assessed by C-urea breath test and/or histology at least 4 weeks after therapy. Intention to treat and per protocol analyses of the eradication rates were performed. Secondary endpoints included patient adherence, safety, and the impact of prior antibiotic exposure in treatment efficacy. RESULTS: The overall eradication rates of the 2 treatments were 87.9% versus 87.4% in the intention to treat analysis, P=1.000, and 93% versus 94.1%, P=0.859, in the per protocol analysis for the 10-day and the 14-day treatment group, respectively. Both groups displayed excellent compliance rates (99.5% for the 10-day vs. 96.2% for the 14-day treatment duration, P=0.067). As regards treatment safety, serious adverse events that led to the discontinuation of both regimens were few, with no statistical difference between the 2 groups (0.5% in the 10-day group and 2.2% in the 14-day group, P>0.05). Previous antibiotic exposure was not significant with regard to treatment efficacy. CONCLUSION: In Greece, the 10-day concomitant nonbismuth quadruple regimen for first-line treatment remains the most efficient strategy for H. pylori eradication.

Sinus Bradycardia During Targeted Temperature Management: A Systematic Review and Meta-Analysis.

The beneficial effect of sinus bradycardia during targeted temperature management (TTM) in cardiac arrest patients remains doubtful. We aimed to investigate the impact of sinus bradycardia on survival and neurological outcome. MEDLINE (PubMed), Cochrane, Google Scholar, and ClinicalTrials.gov databases were searched for studies reporting on comatose postcardiac arrest patients presenting sinus bradycardia during TTM. Outcomes were the 180-day survival and final neurologic function assessed by the Cerebral Performance Category scale. The effect size on study outcomes is presented as odds ratio (OR) with 95% confidence interval (CI). Two studies with 681 patients were included. Compared to no-sinus bradycardia group, in patients with sinus bradycardia below 50 bpm, a significant effect of sinus bradycardia on reduction of 180-day mortality was reported (OR = 0.42; 95% CI: 0.29-0.59). No heterogeneity was detected. Sinus bradycardia below 50 bpm during TTM may be protective and should be considered in comatose postcardiac arrest patients.

Size does matter: when a large plastic biliary stent ends up in the root of the mesentery.

Duodenal perforations due to biliary stenting migration, although rare, can occur. We report a unique case of duodenal perforation due to a large in length plastic stent with no (or marginal) migration, which ended up in the root of the mesentery, explaining the normal laboratory values and minimal imaging findings observed. Any clinical symptom during the postprocedural period should raise the suspicion of a major complication and prompt quick management decisions.

Quality of life in adults with cystic fibrosis: the Greek experience.

INTRODUCTION: Recent developments in treatment have steadily raised the median predicted age of survival for people with Cystic Fibrosis (CF). We report the health-related quality of life (HRQoL) in CF adult patients and correlate our findings with the patients' demographic characteristics. MATERIAL AND METHODS: The Cystic Fibrosis Quality of Life (CFQoL) questionnaire was answered by 77 CF adult patients. The questionnaire included questions pertaining to age, sex and level of education and covered eight sections of functioning. RESULTS: The highest score was reported in the "Social Functioning" section, while the lowest in the "Concerns for the Future" section. When different age groups were compared, statistical significances were reported in "Physical Functioning", "Interpersonal Relationships", and the "Career Concerns" section, with older patients reporting statistically higher HRQoL scores than younger ones (p < 0.005). No statistically significant difference was reported amongst the scoring between male and female CF patients. When different educational levels were compared, patients that had received a higher educational training scored statistically higher in all but one sections of the questionnaire when compared with patients of a lower educational level (p < 0.005). CONCLUSION: More than half Greek adult CF patients report that they are capable to participate in social activities but most of them are worried about the outcome of their disease and its effect on their lives.

Concomitant versus sequential therapy for the treatment of Helicobacter pylori infection: a Greek randomized prospective study.

OBJECTIVE: The objective of this study is to compare, in Greece, a region with >20% local resistance to clarithromycin, the efficacy rates of the concomitant versus the sequential H. pylori eradication therapy. MATERIALS AND METHODS: Our prospective randomized study included 364 patients with newly diagnosed H. pylori infection, randomized to receive a 10-day concomitant or 10-day sequential therapy. Treatment outcome was assessed by C(13)-urea breath test at least 4 weeks after therapy. Intention to treat (ITT) and per protocol (PP) analysis of the eradication rates were performed. Secondary end points included patient compliance and safety. RESULTS: The concomitant therapy group achieved statistically significant higher eradication rates when compared with the sequential treatment group, both in the ITT and in the PP analysis (84.6% versus 70.9%, p = 0.002, and 90.6% versus 78.1%, p = 0.001, respectively), after adjusting for age, gender, smoking status, and the presence or not of ulcer and/or non-ulcer dyspepsia. Both groups displayed excellent compliance rates (99.5% for the concomitant therapy group and 96.2% for the sequential therapy group, p = 0.067). Regarding treatment safety, major adverse events that led to the discontinuation of both regimens were few, with no statistical difference between the two groups (7.0% for the concomitant therapy group and 2.9% for the sequential therapy group). CONCLUSIONS: Concomitant therapy led to statistically significant higher eradication rates over sequential therapy. Both therapies showed excellent compliance and an acceptable safety profile. The 10-day quadruple concomitant scheme should be the adopted for first-line H. pylori eradication in Greece.

Cardiopulmonary resuscitation: a historical perspective leading up to the end of the 19th century.

Social laws and religious beliefs throughout history underscore the leaps and bounds that the science of resuscitation has achieved from ancient times until today. The effort to resuscitate victims goes back to ancient history, where death was considered a special form of sleep or an act of God. Biblical accounts of resuscitation attempts are numerous. Resuscitation in the Middle Ages was forbidden, but later during Renaissance, any prohibition against performing cardiopulmonary resuscitation (CPR) was challenged, which finally led to the Enlightenment, where scholars attempted to scientifically solve the problem of sudden death. It was then that the various components of CPR (ventilation, circulation, electricity, and organization of emergency medical services) began to take shape. The 19th century gave way to hallmarks both in the ventilatory support (intubation innovations and the artificial respirator) and the open-and closed chest circulatory support. Meanwhile, novel defibrillation techniques had been employed and ventricular fibrillation described. The groundbreaking discoveries of the 20th century finally led to the scientific framework of CPR. In 1960, mouth-to-mouth resuscitation was eventually combined with chest compression and defibrillation to become CPR as we now know it. This review presents the scientific milestones behind one of medicine's most widely used fields.

Commonest overgrowth syndromes.

Overgrowth syndromes, although rare, are diagnosed more frequently lately. Major progress, such as the identification of genetic causes, has recently enhanced the delineation of the characteristic and noncharacteristic manifestations, phenotype-genotype correlations and knowledge of the underlying pathophysiologic mechanisms. This review provides a summary of the most important overgrowth syndromes aiming to familiarize the treating physician with the cardinal clinical features involved in these syndromes that encompass overgrowth, but also have a variety of other clinical manifestations (neurologic, musculoskeletal, skin, and accompanying tumors).