ABSTRACT The aim of this study was to assess the efficacy and safety of hybrid closed-loop (HCL) systems for insulin delivery in children and adolescents with type 1 diabetes (T1D). We searched Embase, PubMed, and Cochrane Library for randomized controlled trials (RCTs) published until March 2023 comparing the HCL therapy with control therapies for children and adolescents with T1D. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) with 95% confidence intervals (CIs) for binary endpoints. Four RCTs and 501 patients were included, of whom 323 were randomized to HCL therapy. Compared with control therapies, HCL significantly improved the period during which glucose level was 70-180 mg/dL (WMD 10.89%, 95% CI 8.22-13.56%) and the number of participants with glycated hemoglobin (HbA1c) level < 7% (RR 2.61, 95% CI 1.29-5.28). Also, HCL significantly reduced the time during which glucose level was > 180 mg/dL (WMD -10.46%, 95% CI -13.99 to -6.93%) and the mean levels of glucose (WMD -16.67 mg/dL, 95% CI -22.25 to -11.09 mg/dL) and HbA1c (WMD -0.50%, 95% CI -0.68 to -0.31). There were no significant differences between therapies regarding time during which glucose level was < 70 mg/dL or <54 mg/dL or number of episodes of ketoacidosis, hyperglycemia, and hypoglycemia. In this meta-analysis, HCL compared with control therapies was associated with improved time in range and HbA1c control in children and adolescents with T1D and a similar profile of side effects. These findings support the efficacy of HCL in the treatment of T1D in this population. closedloop closed loop (HCL TD . T D (T1D) Embase PubMed (RCTs 202 WMDs (WMDs RRs (RRs 95 CIs (CIs endpoints 50 included 32 70180 70-18 mgdL mg dL WMD 1089 10 89 10.89% 8.2213.56% 8221356 8.22 13.56% 8 22 13 56 8.22-13.56% HbAc HbA c (HbA1c 7 RR 261 2 61 2.61 1.295.28. 129528 1.29 5.28 29 5 28 1.29-5.28) Also 18 10.46%, 1046 46 -10.46% 13.99 1399 99 -13.9 6.93% 693 6 93 -6.93% 16.67 1667 16 67 -16.6 22.25 2225 25 -22.2 11.09 1109 11 09 -11.0 0.50%, 050 0 -0.50% 0.68 068 68 -0.6 0.31. 031 0.31 31 -0.31) 54 <5 ketoacidosis hyperglycemia hypoglycemia metaanalysis, metaanalysis meta analysis, analysis meta-analysis effects population (T1D 20 9 3 7018 70-1 108 10.89 2213 8.2213.56 822135 822 8.2 1356 13.56 8.22-13.56 26 2.6 295 1.295.28 12952 129 1.2 528 5.2 1.29-5.28 10.46% 104 4 -10.46 13.9 139 -13. 6.93 69 -6.93 16.6 166 -16. 22.2 222 -22. 11.0 110 -11. 0.50% 05 -0.50 0.6 06 -0. 03 0.3 -0.31 701 70- 10.8 221 8.2213.5 82213 82 8. 135 13.5 8.22-13.5 2. 1.295.2 1295 12 1. 52 5. 1.29-5.2 10.46 -10.4 13. -13 6.9 -6.9 16. -16 22. -22 11. -11 0.50 -0.5 0. -0 -0.3 10. 8.2213. 8221 8.22-13. 1.295. 1.29-5. 10.4 -10. -1 6. -6. -2 0.5 - 8.2213 8.22-13 1.295 1.29-5 -10 -6 8.221 8.22-1 1.29- 8.22-

Resumo Fundamento Os antagonistas da vitamina K (AVKs) são o tratamento de primeira linha recomendado para trombo ventricular esquerdo (TVE); entretanto, os anticoagulantes orais diretos (AODs) têm sido considerados uma terapia alternativa. Objetivos Avaliar a eficácia e a segurança dos AODs em comparação com a terapia com AVKs em pacientes com TVE. Métodos PubMed, Embase e Cochrane foram sistematicamente pesquisados em busca de ensaios clínicos randomizados ou estudos de coorte que comparassem AODs versus AVKs para TVE. As razões de risco (RR) foram calculadas para desfechos binários, com intervalos de confiança (IC) de 95%. A significância estatística foi definida como valor de p < 0,05. Resultados Foram incluídos um total de 4 ensaios clínicos randomizados e 29 estudos de coorte, com 4.450 pacientes designados para AODs ou AVKs. Não houve diferença significativa entre os grupos para acidente vascular cerebral ou eventos embólicos sistêmicos (AVC/EES) (RR 0,84; IC 95% 0,65 a 1,07; p = 0,157), acidente vascular cerebral (RR 0,73; IC 95% 0,48 a 1,11; p = 0,140), eventos embólicos sistêmicos (EES) (RR 0,69; IC 95% 0,40 a 1,17; p = 0,166), resolução do trombo (RR 1,05; IC 95% 0,99 a 1,11; p = 0,077), qualquer sangramento (RR 0,78; IC 95% 0,60 a 1,00; p = 0,054), sangramento clinicamente relevante (RR 0,69; IC 95% 0,46 a 1,03; p = 0,066), sangramento menor (RR 0,73; IC 95% 0,43 a 1,23; p = 0,234), sangramento maior (RR 0,87; IC 95% 0,42 a 1,80; p = 0,705) e mortalidade por todas as causas (RR 1,05; IC 95% 0,79 a 1,39; p = 0,752). Em comparação com AVKs, a rivaroxabana reduziu significativamente AVC/EES (RR 0,35; IC 95% 0,16 a 0,91; p = 0,029) e EES (RR 0,39; IC 95% 0,16 a 0,95; p = 0,037). Conclusões Os AODs tiveram uma taxa semelhante de eventos tromboembólicos e hemorrágicos, bem como de resolução do trombo, em comparação com os AVKs no tratamento de TVE. A terapia com rivaroxabana teve uma redução significativa nos eventos tromboembólicos, em comparação com os AVKs. (AVKs TVE (TVE) entretanto (AODs alternativa PubMed RR binários (IC 95 005 0 05 0,05 2 4450 450 4.45 AVCEES AVC (AVC/EES 0,84 084 84 065 65 0,6 1,07 107 1 07 0,157, 0157 0,157 , 157 0,157) 0,73 073 73 048 48 0,4 1,11 111 11 0,140, 0140 0,140 140 0,140) (EES 0,69 069 69 040 40 1,17 117 17 0,166, 0166 0,166 166 0,166) 1,05 105 099 99 0,9 0,077, 0077 0,077 077 0,077) 0,78 078 78 060 60 1,00 100 00 0,054, 0054 0,054 054 0,054) 046 46 1,03 103 03 0,066, 0066 0,066 066 0,066) 043 43 1,23 123 23 0,234, 0234 0,234 234 0,234) 0,87 087 87 042 42 1,80 180 80 0,705 0705 705 079 79 0,7 1,39 139 39 0,752. 0752 0,752 . 752 0,752) 0,35 035 35 016 16 0,1 0,91 091 91 0,029 0029 029 0,39 039 0,95 095 0,037. 0037 0,037 037 0,037) hemorrágicos (TVE 9 0,0 445 45 4.4 0,8 08 8 06 6 0, 1,0 10 015 0,15 15 7 04 1,1 014 0,14 14 09 007 0,07 006 0,06 1,2 12 023 0,23 1,8 18 0,70 070 70 1,3 13 3 075 0,75 75 0,3 01 0,02 002 02 003 0,03 44 4. 1, 0,2

Abstract Background Vitamin K antagonists (VKAs) are the recommended first-line treatment for left ventricular thrombus (LVT); however, direct oral anticoagulants (DOACs) have been considered an alternative therapy. Objectives To evaluate the efficacy and safety of DOACs compared with VKAs therapy in patients with LVT. Methods PubMed, Embase, and Cochrane were systematically searched for randomized clinical trials or cohort studies that compared DOACs versus VKAs for LVT. Risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (95% CIs). Statistical significance was defined as p value < 0.05. Results A total of 4 randomized clinical trials and 29 cohort studies were included, with 4,450 patients assigned to either DOACs or VKAs. There was no significant difference between groups for stroke or systemic embolic (SSE) events (RR 0.84; 95% CI 0.65 to 1.07; p = 0.157), stroke (RR 0.73; 95% CI 0.48 to 1.11; p = 0.140), systemic embolic (SE) events (RR 0.69; 95% CI 0.40 to 1.17; p = 0.166), thrombus resolution (RR 1.05; 95% CI 0.99 to 1.11; p = 0.077), any bleeding (RR 0.78; 95% CI 0.60 to 1.00; p = 0.054), clinically relevant bleeding (RR 0.69; 95% CI 0.46 to 1.03; p = 0.066), minor bleeding (RR 0.73; 95% CI 0.43 to 1.23; p = 0.234), major bleeding (RR 0.87; 95% CI 0.42 to 1.80; p = 0.705), and all-cause mortality (RR 1.05; 95% CI 0.79 to 1.39; p = 0.752). Compared with VKAs, rivaroxaban significantly reduced SSE events (RR 0.35; 95% CI 0.16 to 0.91; p = 0.029) and SE events (RR 0.39; 95% CI 0.16 to 0.95; p = 0.037). Conclusions DOACs had a similar rate of thromboembolic and hemorrhagic events, as well as thrombus resolution, compared to VKAs in the treatment of LVTs. Rivaroxaban therapy had a significant reduction in thromboembolic events, compared to VKAs. (VKAs firstline first line LVT (LVT) however (DOACs PubMed Embase RRs (RRs endpoints 95 (95 CIs. CIs . CIs) 005 0 05 0.05 2 included 4450 450 4,45 (SSE RR 0.84 084 84 065 65 0.6 1.07 107 1 07 0.157, 0157 0.157 , 157 0.157) 0.73 073 73 048 48 0.4 1.11 111 11 0.140, 0140 0.140 140 0.140) (SE 0.69 069 69 040 40 1.17 117 17 0.166, 0166 0.166 166 0.166) 1.05 105 099 99 0.9 0.077, 0077 0.077 077 0.077) 0.78 078 78 060 60 1.00 100 00 0.054, 0054 0.054 054 0.054) 046 46 1.03 103 03 0.066, 0066 0.066 066 0.066) 043 43 1.23 123 23 0.234, 0234 0.234 234 0.234) 0.87 087 87 042 42 1.80 180 80 0.705, 0705 0.705 705 0.705) allcause all cause 079 79 0.7 1.39 139 39 0.752. 0752 0.752 752 0.752) 0.35 035 35 016 16 0.1 0.91 091 91 0.029 0029 029 0.39 039 0.95 095 0.037. 0037 0.037 037 0.037) LVTs (LVT 9 (9 0.0 445 45 4,4 0.8 08 8 06 6 0. 1.0 10 015 0.15 15 7 04 1.1 014 0.14 14 09 007 0.07 006 0.06 1.2 12 023 0.23 1.8 18 070 0.70 70 1.3 13 3 075 0.75 75 0.3 01 0.02 002 02 003 0.03 ( 44 4, 1. 0.2

RESUMO RACIONAL: O bypass gástrico de uma anastomose (BGU tem ganhado destaque na busca por melhores resultados na cirurgia bariátrica. No entanto, a eficácia e segurança do BGUA, em relação ao bypass gástrico em Y de Roux (BGYR) e à gastrectomia vertical (GV), permanecem imprecisas. OBJETIVOS: Comparar a eficácia e segurança do BGUA em relação ao BGYR e GV no tratamento da obesidade. MÉTODOS: Realizamos uma busca sistemática nas bases de dados do PubMed, EMBASE, Cochrane, Lilacs e Google Scholar por ensaios clínicos randomizados que comparassem o BGUA ao BGYR ou GV na abordagem cirúrgica da obesidade. Agrupamos resultados para índice de massa corporal, porcentagem da perda de peso em excesso, remissão do diabetes mellitus tipo 2, complicações e taxas de doença do refluxo gastroesofágico. As análises estatísticas foram realizadas empregando o software R, versão 4.2.3. RESULTADOS: Dados de 854 pacientes foram extraídos de 11 ensaios clínicos randomizados, dos quais 422 (49,4%) foram submetidos ao BGUA, com seguimento médio variando de seis meses a cinco anos. Na análise combinada, o BGUA esteve associado a uma porcentagem da perda de peso em excesso significativamente maior no acompanhamento de um ano e a um índice de massa corporal significativamente menor no acompanhamento de cinco anos em pacientes submetidos ao BGUA. Por outro lado, as taxas de remissão da diabetes mellitus tipo 2, de complicações e da doença do refluxo gastroesofágico não foram significativamente diferentes entre os grupos. A qualidade geral das evidências foi considerada muito baixa. CONCLUSÕES: Nossos resultados corroboram a eficácia comparável do BGUA em relação ao BGYR e GV no tratamento da obesidade, mantendo diferenças não significativas nas taxas de remissão da diabetes mellitus tipo 2, complicações e doença do refluxo gastroesofágico. RACIONAL BGU bariátrica entanto (BGYR GV, , (GV) imprecisas OBJETIVOS obesidade MÉTODOS PubMed EMBASE Cochrane 2 R 423 4 3 4.2.3 RESULTADOS 85 1 42 49,4% 494 49 (49,4% combinada lado grupos baixa CONCLUSÕES (GV 4.2. 8 49,4 (49,4 4.2 49, (49, 4. (49 (4 (

ABSTRACT BACKGROUND: One anastomosis gastric bypass (OAGB) has gained prominence in the search for better results in bariatric surgery. However, its efficacy and safety compared to Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) remain ill-defined. AIMS: To compare the efficacy and safety of OAGB relative to RYGB and SG in the treatment of obesity. METHODS: We systematically searched PubMed, EMBASE, Cochrane Library, Lilacs, and Google Scholar databases for randomized controlled trials comparing OAGB with RYGB or SG in the surgical approach to obesity. We pooled outcomes for body mass index, percentage of excess weight loss, type-2 diabetes mellitus remission, complications, and gastroesophageal reflux disease. Statistical analyses were performed with R software (version 4.2.3). RESULTS: Data on 854 patients were extracted from 11 randomized controlled trials, of which 422 (49.4%) were submitted to OAGB with mean follow-up ranging from six months to five years. The meta-analysis revealed a significantly higher percentage of excess weight loss at 1-year follow-up and a significantly lower body mass index at 5-year follow-up in OAGB patients. Conversely, rates of type-2 diabetes mellitus remission, complications, and gastroesophageal reflux disease were not significantly different between groups. The overall quality of evidence was considered very low. CONCLUSIONS: Our results corroborate the comparable efficacy of OAGB in relation to RYGB and SG in the treatment of obesity, maintaining no significant differences in type-2 diabetes mellitus remission, complications, and gastroesophageal reflux disease rates. BACKGROUND (OAGB surgery However RouxenY Roux en Y (RYGB (SG illdefined. illdefined ill defined. defined ill-defined AIMS obesity METHODS PubMed EMBASE Library Lilacs type2 type 2 type- remission complications version 4.2.3. 423 4.2.3 . 4 3 4.2.3) RESULTS 85 1 42 49.4% 494 49 (49.4% followup follow up years metaanalysis meta analysis 1year year 5year 5 Conversely groups low CONCLUSIONS 4.2. 8 49.4 (49.4 4.2 49. (49. 4. (49 (4 (

ABSTRACT The aim of this study is to assess the effects of once-daily oral orforglipron on weight and metabolic markers in adult patients. PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were systematically searched until February 2024 for randomized controlled trials (RCTs) comparing orforglipron versus placebo or other anti-obesity medications in adult patients. Weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) or risk differences for binary endpoints were computed, with 95% confidence intervals (CIs). Heterogeneity and risk of bias were assessed with I2 statistics and Rob-2, respectively. Statistical analyses were performed using R, version 4.2.2. A total of four studies were included, comprising 815 patients, of whom 620 (76.1%) were prescribed orforglipron. Compared with placebo, orforglipron reduced body weight (WMD -6.14 kg, 95% CI -9.62 to -2.66 kg), body mass index (WMD -2.87 kg/m2, 95% CI -4.65 to -1.10 kg/m2), and waist circumference (WMD -5.32 cm, 95% CI -9.13 to -1.51 cm). More patients treated with orforglipron than placebo achieved a weight loss of ≥ 5% (RR 3.31, 95% CI 2.23-4.93), ≥ 10% (RR 5.24, 95% CI 2.07-13.31), and ≥ 15% (RR 9.53, 95% CI 1.26-71.89). The most common adverse events were related to the gastrointestinal tract. In this meta-analysis, the use of once-daily oral orforglipron by adult patients was associated with a significant decrease in body weight, as compared with placebo, with an increase in non-severe gastrointestinal adverse events. Phase 3 RCTs are expected to shed further light on the efficacy and safety of once-daily oral orforglipron over the long term. oncedaily once daily PubMed Embase Library ClinicalTrialsgov ClinicalTrials gov 202 (RCTs antiobesity anti obesity WMDs (WMDs RRs (RRs computed 95 CIs. CIs . (CIs) I Rob2, Rob2 Rob 2, 2 Rob-2 respectively R 422 4 4.2.2 included 81 62 76.1% 761 76 1 (76.1% WMD 6.14 614 6 14 -6.1 kg 9.62 962 9 -9.6 2.66 266 66 -2.6 , kg) 2.87 287 87 -2.8 kgm2 kgm m2 m kg/m2 4.65 465 65 -4.6 1.10 110 10 -1.1 kg/m2) 5.32 532 5 32 -5.3 cm 9.13 913 13 -9.1 1.51 151 51 -1.5 cm. cm) RR 331 31 3.31 2.234.93, 223493 2.23 4.93 23 93 2.23-4.93) 524 24 5.24 2.0713.31, 2071331 2.07 13.31 07 2.07-13.31) 15 953 53 9.53 1.2671.89. 1267189 1.26 71.89 26 71 89 1.26-71.89) tract metaanalysis, metaanalysis meta analysis, analysis meta-analysis nonsevere non severe term 20 (CIs Rob- 42 4.2. 8 76.1 7 (76.1 6.1 61 -6. 9.6 96 -9. 2.6 -2. 2.8 28 kg/m 4.6 46 -4. 1.1 11 -1. 5.3 -5. 9.1 91 1.5 33 3.3 234 2.234.93 22349 223 2.2 493 4.9 2.23-4.93 52 5.2 0713 2.0713.31 207133 207 2.0 1331 13.3 0 2.07-13.31 9.5 2671 1.2671.89 126718 126 1.2 7189 71.8 1.26-71.89 4.2 76. (76. 6. -6 9. -9 2. -2 4. -4 1. -1 5. -5 3. 2.234.9 2234 22 49 2.23-4.9 071 2.0713.3 20713 133 13. 2.07-13.3 267 1.2671.8 12671 12 718 71. 1.26-71.8 (76 - 2.234. 2.23-4. 2.0713. 2071 2.07-13. 1.2671. 1267 1.26-71. (7 2.234 2.23-4 2.0713 2.07-13 1.2671 1.26-71 ( 2.23- 2.071 2.07-1 1.267 1.26-7 2.07- 1.26-