Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials.

OBJECTIVES: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes. We performed a meta-analysis to assess tirzepatide's weight reduction efficacy and safety. METHODS: We searched PubMed, Embase, and Cochrane for randomized controlled trials published from inception to July 2022, comparing tirzepatide with placebo for the co-primary endpoints of absolute and percent change in weight. Mean difference (MD) and odds ratio (OR) were calculated for continuous and binary outcomes, respectively. Review Manager 5.4.1 and RStudio were used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. RESULTS: Of 397 search results, 6 studies (4036 participants) ranging from 12 to 72 weeks were included. Pooled analysis showed that tirzepatide 5 mg, 10 mg, and 15 mg were more effective than placebo, with MD in body weight of -7.7 kg (95% CI -11.0, -4.4; p < 0.001), -11.6 kg (95% CI -18.8, -4.3; p = 0.002), and -11.8 kg (95% CI -17.4, -6.2; p < 0.001), respectively, and MD in percent change in weight of -8.1% (95% CI -11.0, -5.2; p < 0.001), -11.9% (95% CI -18.1, -5.6; p < 0.001), and -12.4% (95% CI -17.2, -7.5; p < 0.001), respectively. Tirzepatide also reduced BMI and waist circumference. Adverse events were more common with tirzepatide with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p < 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p < 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p < 0.001) (15 mg dose), when compared with placebo. CONCLUSIONS: The results support that tirzepatide leads to substantial weight reduction and constitutes a valuable therapeutic option for weight management, despite an increase in gastrointestinal symptoms. PROTOCOL REGISTRATION: CRD42022348576.

A Rodential Reckoning: A Case Report and Systematic Review of Streptobacillary Endocarditis.

Introduction: Endocarditis is a rare, often fatal complication of rat bite fever caused by Streptobacillus moniliformis. Only 39 cases have been reported (including this case) as of 2022. We describe a case and aim to perform this entit's first systematic literature review. Methods: We performed a systematic review in CENTRAL, EMBASE, MEDLINE, SciELO, and LILACS. The terms used were terms used were (but not limited to) rat bite fever, Streptobacillus moniliformis, Spirillum minus, and endocarditis. We included all abstracts and articles with patients with echocardiographic or histologic-proven endocarditis. In case of discordance, a third reviewer was involved. Our protocol was submitted to PROSPERO (CRD42022334092). We also performed searches for studies on the reference list of included articles. Results: We retrieved 108 and included 36 abstracts and articles. A total of 39 patients (including our report) were identified. The mean age was 41.27, and 61.5% were males. The most common findings were fever, murmur, arthralgias, fatigue, splenomegaly, and rash. Underlying heart disease was present in 33%. Exposure to rats was noted in 71.8% of patients, with 56.4% recalling a rat bite. Anemia was seen in 57%, leukocytosis in 52%, and elevated inflammatory markers in 58% that had lab work performed. The mitral valve was most affected, followed by the aortic, tricuspid, and pulmonary valves. Surgical intervention was required in 14 (36%) cases. Of those, 10 required valve replacement. Death was reported in 36% of cases. Unfortunately, the literature available is limited to case series and reports. Conclusion: Our review allows clinicians to suspect better, diagnose, and manage Streptobacillary endocarditis.

A Rodential Reckoning: A Case Report and Systematic Review of Streptobacillary Endocarditis

ABSTRACT Introduction Endocarditis is a rare, often fatal complication of rat bite fever caused by Streptobacillus moniliformis. Only 39 cases have been reported (including this case) as of 2022. We describe a case and aim to perform this entit's first systematic literature review. Methods We performed a systematic review in CENTRAL, EMBASE, MEDLINE, SciELO, and LILACS. The terms used were terms used were (but not limited to) rat bite fever, Streptobacillus moniliformis, Spirillum minus, and endocarditis. We included all abstracts and articles with patients with echocardiographic or histologic-proven endocarditis. In case of discordance, a third reviewer was involved. Our protocol was submitted to PROSPERO (CRD42022334092). We also performed searches for studies on the reference list of included articles. Results We retrieved 108 and included 36 abstracts and articles. A total of 39 patients (including our report) were identified. The mean age was 41.27, and 61.5% were males. The most common findings were fever, murmur, arthralgias, fatigue, splenomegaly, and rash. Underlying heart disease was present in 33%. Exposure to rats was noted in 71.8% of patients, with 56.4% recalling a rat bite. Anemia was seen in 57%, leukocytosis in 52%, and elevated inflammatory markers in 58% that had lab work performed. The mitral valve was most affected, followed by the aortic, tricuspid, and pulmonary valves. Surgical intervention was required in 14 (36%) cases. Of those, 10 required valve replacement. Death was reported in 36% of cases. Unfortunately, the literature available is limited to case series and reports. Conclusion Our review allows clinicians to suspect better, diagnose, and manage Streptobacillary endocarditis.

Phenotypes of sickle cell intensive care admissions: an unsupervised machine learning approach in a single-center retrospective cohort.

Sickle cell disease (SCD) is associated with multiple known complications and increased mortality. This study aims to further understand the profile of intensive care unit (ICU) admissions of SCD patients. In this single-center retrospective cohort (approval number 0926-11), we evaluated SCD-related ICU admissions at our hospital in São Paulo, Brazil. Admissions were clustered using clinical data and organ dysfunction at ICU admission. A hierarchical clustering method was used to distinguish phenotypes. From 140 admissions obtained, 125 were included. The mean age was 30 years, 48% were male, and SS genotype was predominant (71.2%). Non-surgical causes of admissions accounted for 85.6% (n = 107). The mean Sequential Organ Failure Assessment score (SOFA) was 4 (IQR 2-7). Vasopressors were required by 12% and mechanical ventilation by 17.6%. After analysis of the average silhouette width, the optimal number of clusters was 3: cluster 1 (n = 69), cluster 2 (n = 25), cluster 3 (n = 31). Cluster 1 had a mean age of 29 years, 87% of SS genotype, and mean SOFA of 4. Cluster 2 had a mean age of 37 years, 80% of SS genotype, and mean SOFA of 8. Cluster 3 had a mean age of 26 years, 29% of SS genotype, and mean SOFA of 3. The need for mechanical ventilation was 11.6%, 44%, and 9.7%, respectively. Mortality was significantly higher in cluster 2 (44%, p = 0.012). This cohort of critical SCD admissions suggested the presence of three different profiles. This can be informative in the ICU setting to identify SCD patients at higher risk of worse outcomes.

Pulmonary Alveolar Proteinosis due to Familial Myelodysplastic Syndrome with resolution after stem cell transplant.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease with an incidence of 0.2 cases per million. PAP has multiple causes, including autoimmune, hereditary, congenital, or secondary. The latter includes hematologic conditions and exposure to different kinds of dust. Most patients present fever, dyspnea, and cough. The chest computed tomography (CT) may reveal the crazy-paving polygonal shapes with superimposed ground glass opacities delimited by thickened interlobular septa; however, this finding is more prevalent in patients with autoimmune PAP. Bronchoalveolar lavage (BAL) shows a milky-opaque appearance with PAS-positive debris on cytology. Treatment is focused on the underlying disease; however, some patients may require whole lung lavage for symptomatic management. We report a case of a 30-year-old female with a history of familial myelodysplastic syndrome (MDS) with GATA 2 mutation who presented to the outpatient clinic with several months of progressive dyspnea and nonproductive cough. The chest CT revealed bilateral ground-glass opacities prominently in the upper lobes. She underwent a bronchoscopy with lavage and biopsy, which revealed fragments of lung parenchyma with intra-alveolar coarse granular eosinophilic material strongly positive for PAS and d-PAS. The overall clinical presentation and histologic findings were diagnostic of PAP. Her GM-CSF was negative, and due to her history of MDS, secondary PAP (S-PAP) was strongly suspected. She underwent a successful allogeneic bone marrow pluripotent stem cell transplant to treat the myelodysplastic syndrome, with a follow-up chest CT showing clear lung parenchyma. The patient had resolution of symptoms about four months after the bone marrow transplant, confirming the diagnosis of S-PAP.

Pulmonary Alveolar Proteinosis due to Familial Myelodysplastic Syndrome with resolution after stem cell transplant

ABSTRACT Pulmonary alveolar proteinosis (PAP) is a rare lung disease with an incidence of 0.2 cases per million. PAP has multiple causes, including autoimmune, hereditary, congenital, or secondary. The latter includes hematologic conditions and exposure to different kinds of dust. Most patients present fever, dyspnea, and cough. The chest computed tomography (CT) may reveal the crazy-paving polygonal shapes with superimposed ground glass opacities delimited by thickened interlobular septa; however, this finding is more prevalent in patients with autoimmune PAP. Bronchoalveolar lavage (BAL) shows a milky-opaque appearance with PAS-positive debris on cytology. Treatment is focused on the underlying disease; however, some patients may require whole lung lavage for symptomatic management. We report a case of a 30-year-old female with a history of familial myelodysplastic syndrome (MDS) with GATA 2 mutation who presented to the outpatient clinic with several months of progressive dyspnea and nonproductive cough. The chest CT revealed bilateral ground-glass opacities prominently in the upper lobes. She underwent a bronchoscopy with lavage and biopsy, which revealed fragments of lung parenchyma with intra-alveolar coarse granular eosinophilic material strongly positive for PAS and d-PAS. The overall clinical presentation and histologic findings were diagnostic of PAP. Her GM-CSF was negative, and due to her history of MDS, secondary PAP (S-PAP) was strongly suspected. She underwent a successful allogeneic bone marrow pluripotent stem cell transplant to treat the myelodysplastic syndrome, with a follow-up chest CT showing clear lung parenchyma. The patient had resolution of symptoms about four months after the bone marrow transplant, confirming the diagnosis of S-PAP.

Usefulness of ECG criteria to rule out left ventricular hypertrophy in older individuals with true left bundle branch block: an observational study.

BACKGROUND: Advanced age is associated with both left bundle branch block (LBBB) and hypertension and the usefulness of ECG criteria to detect left ventricular hypertrophy (LVH) in patients with LBBB is still unclear. The diagnostic performance and clinical applicability of ECG-based LVH criteria in patients with LBBB defined by stricter ECG criteria is unknown. The aim of this study was to compare diagnostic accuracy and clinical utility of ECG criteria in patients with advanced age and strict LBBB criteria. METHODS: Retrospective single-center study conducted from Jan/2017 to Mar/2018. Patients undergoing both ECG and echocardiogram examinations were included. Ten criteria for ECG-based LVH were compared using LVH defined by the echocardiogram as the gold standard. Sensitivity, specificity, predictive values, likelihood ratios, AUC, and the Brier score were used to compare diagnostic performance and a decision curve analysis was performed. RESULTS: From 4621 screened patients, 68 were included, median age was 78.4 years, (IQR 73.3-83.4), 73.5% with hypertension. All ECG criteria failed to provide accurate discrimination of LVH with AUC range between 0.54 and 0.67, and no ECG criteria had a balanced tradeoff between sensitivity and specificity. No ECG criteria consistently improved the net benefit compared to the strategy of performing routine echocardiogram in all patients in the decision curve analysis within the 10-60% probability threshold range. CONCLUSION: ECG-based criteria for LVH in patients with advanced age and true LBBB lack diagnostic accuracy or clinical usefulness and should not be routinely assessed.

Clinical applicability and diagnostic performance of electrocardiographic criteria for left ventricular hypertrophy diagnosis in older adults.

Recently, a new ECG criterion, the Peguero-Lo Presti (PLP), improved overall accuracy in the diagnosis of left ventricular hypertrophy (LVH)-compared to traditional ECG criteria, but with few patients with advanced age. We analyzed patients with older age and examined which ECG criteria would have better overall performance. A total of 592 patients were included (83.1% with hypertension, mean age of 77.5 years) and the PLP criterion was compared against Cornell voltage (CV), Sokolow-Lyon voltage (SL) and Romhilt-Estes criteria (cutoffs of 4 and 5 points, RE4 and RE5, respectively) using LVH defined by the echocardiogram as the gold standard. The PLP had higher AUC than the CV, RE and SL (respectively, 0.70 vs 0.66 vs 0.64 vs 0.67), increased sensitivity compared with the SL, CV and RE5 (respectively, 51.9% [95% CI 45.4-58.3%] vs 28.2% [95% CI 22.6-34.4%], p < 0.0001; vs 35.3% [95% CI 29.2-41.7%], p < 0.0001; vs 44.4% [95% CI 38.0-50.9%], p = 0.042), highest F1 score (58.3%) and net benefit for most of the 20-60% threshold range in the decision curve analysis. Overall, despite the best diagnostic performance in older patients, the PLP criterion cannot rule out LVH consistently but can potentially be used to guide clinical decision for echocardiogram ordering in low-resource settings.

First-attempt intubation success and complications in patients with COVID-19 undergoing emergency intubation.

Objectives: To evaluate the first-attempt success rates and complications of endotracheal intubation of coronavirus disease 2019 (COVID-19) patients by emergency physicians. Methods: This prospective observational study was conducted from March 24, 2020 through May 28, 2020 at the emergency department (ED) of an urban, academic trauma center. We enrolled patients consecutively admitted to the ED with suspected or confirmed COVID-19 submitted to endotracheal intubation. No patients were excluded. The primary outcome was first-attempt intubation success, defined as successful endotracheal tube placement with the first device passed (endotracheal tube) during the first laryngoscope insertion confirmed with capnography. Secondary outcomes included the following complications: hypotension, hypoxemia, aspiration, and esophageal intubation. Results: A total of 112 patients with confirmed or suspected COVID-19 were enrolled. Median age was 61 years and 61 patients (54%) were men. The primary outcome, first-attempt intubation success, was achieved in 82% of patients. Among the 20 patients who were not intubated on the first attempt, 75% were intubated on the second attempt and 20% on the third attempt; cricothyrotomy was performed in 1 patient. Forty-eight (42%) patients were hypotensive and required norepinephrine immediately post-intubation. Fifty-eight (52%) experienced peri-intubation hypoxemia, and 2 patients (2%) had cardiac arrest. There were no cases of failed intubation resulting in death up to 24 hours after the procedure. Conclusion: Emergency physicians achieve high success rates when intubating COVID19 patients, although complications are frequent. However, these findings should be considered provisional until their generalizability is assessed in their institutions and setting.

Bullous systemic lupus erythematosus - a case report.

Skin involvement in systemic lupus erythematosus (SLE) occurs in more than 75% of patients with this condition. Vesicles and blisters in lupus erythematosus (LE) may be present in SLE secondary to interface vacuolar changes in the epidermis, in discoid LE also secondary to vacuolar epidermal changes, and in bullous LE secondary to antibodies anti-collagen VII deposits with neutrophilic aggregates. In addition, blisters can occur due to the association of SLE with other autoimmune blistering diseases (e.g. bullous pemphigoid). BSLE is a rare blistering disease that mainly occurs in females (30-40 years old), and less frequently in children and adolescents. The most common presentation is rapid and widespread development of tense vesicles and bullae over erythematous macules or plaques. Preferential sites are: superior trunk, proximal superior limbs, and face (lips) with symmetrical distribution. Mucosal involvement is common on perioral, pharyngeal, laryngeal, and genital areas. The involvement of sun-exposed areas is not mandatory. The lesions usually progress with no scarring, but hypo or hyperchromia may be present. We report an 18-year-old female patient with blistering lesions at admission, who was diagnosed with BSLE. She was initially treated with systemic prednisone and hydroxychloroquine. Her condition evolved with relapsing lesions, which required the introduction of Dapsone. The authors emphasize the relevance of recognizing BSLE-a rare presentation of SLE-which may evolve with marked clinical presentation.

Bullous systemic lupus erythematosus ­ a case report

Skin involvement in systemic lupus erythematosus (SLE) occurs in more than 75% of patients with this condition. Vesicles and blisters in lupus erythematosus (LE) may be present in SLE secondary to interface vacuolar changes in the epidermis, in discoid LE also secondary to vacuolar epidermal changes, and in bullous LE secondary to antibodies anti-collagen VII deposits with neutrophilic aggregates. In addition, blisters can occur due to the association of SLE with other autoimmune blistering diseases (e.g. bullous pemphigoid). BSLE is a rare blistering disease that mainly occurs in females (30­40 years old), and less frequently in children and adolescents. The most common presentation is rapid and widespread development of tense vesicles and bullae over erythematous macules or plaques. Preferential sites are: superior trunk, proximal superior limbs, and face (lips) with symmetrical distribution. Mucosal involvement is common on perioral, pharyngeal, laryngeal, and genital areas. The involvement of sun-exposed areas is not mandatory. The lesions usually progress with no scarring, but hypo or hyperchromia may be present. We report an 18-year-old female patient with blistering lesions at admission, who was diagnosed with BSLE. She was initially treated with systemic prednisone and hydroxychloroquine. Her condition evolved with relapsing lesions, which required the introduction of Dapsone. The authors emphasize the relevance of recognizing BSLE­a rare presentation of SLE­which may evolve with marked clinical presentation

Prevalence of gallstones in 1,229 patients submitted to surgical laparoscopic treatment of GERD and esophageal achalasia: associated cholecystectomy was a safe procedure.

BACKGROUND: Association between esophageal achalasia/ gastroesophageal reflux disease (GERD) and cholelithiasis is not clear. Epidemiological data are controversial due to different methodologies applied, the regional differences and the number of patients involved. Results of concomitant cholecistectomy associated to surgical treatment of both diseases regarding safety is poorly understood. AIM: To analyze the prevalence of cholelithiasis in patients with esophageal achalasia and gastroesophageal reflux submitted to cardiomyotomy or fundoplication. Also, to evaluate the safety of concomitant cholecistectomy. METHODS: Retrospective analysis of 1410 patients operated from 2000 to 2013. They were divided into two groups: patients with GERD submitted to laparocopic hiatoplasty plus Nissen fundoplication and patients with esophageal achalasia to laparoscopic cardiomyotomy plus partial fundoplication. It was collected epidemiological data, specific diagnosis and subgroups, the presence or absence of gallstones, surgical procedure, operative and clinical complications and mortality. All groups/subgroups were compared. RESULTS: From 1,229 patients with GERD or esophageal achalasia, submitted to laparoscopic cardiomyotomy or fundoplication, 138 (11.43%) had cholelitiasis, occurring more in females (2.38:1) with mean age of 50,27 years old. In 604 patients with GERD, 79 (13,08%) had cholelitiasis. Lower prevalence occurred in Barrett's esophagus patients 7/105 (6.67%) (p=0.037). In 625 with esophageal achalasia, 59 (9.44%) had cholelitiasis, with no difference between chagasic and idiopathic forms (p=0.677). Complications of patients with or without cholecystectomy were similar in fundoplication and cardiomyotomy (p=0.78 and p=1.00).There was no mortality or complications related to cholecystectomy in this series. CONCLUSIONS: Prevalence of cholelithiasis was higher in patients submitted to fundoplication (GERD). Patients with chagasic or idiopatic forms of achalasia had the same prevalence of cholelithiasis. Gallstones occurred more in GERD patients without Barrett's esophagus. Simultaneous laparoscopic cholecystectomy was proved safe.

Prevalence of gallstones in 1,229 patients submitted to surgical laparoscopic treatment of GERD and esophageal achalasia: associated cholecystectomy was a safe procedure / Prevalência de colelitíase em 1.229 pacientes submetidos ao tratamento cirúrgico laparoscópico de DRGE e megaesôfago: a colecistectomia associada mostra-se segura

BACKGROUND: Association between esophageal achalasia/ gastroesophageal reflux disease (GERD) and cholelithiasis is not clear. Epidemiological data are controversial due to different methodologies applied, the regional differences and the number of patients involved. Results of concomitant cholecistectomy associated to surgical treatment of both diseases regarding safety is poorly understood. AIM: To analyze the prevalence of cholelithiasis in patients with esophageal achalasia and gastroesophageal reflux submitted to cardiomyotomy or fundoplication. Also, to evaluate the safety of concomitant cholecistectomy. METHODS: Retrospective analysis of 1410 patients operated from 2000 to 2013. They were divided into two groups: patients with GERD submitted to laparocopic hiatoplasty plus Nissen fundoplication and patients with esophageal achalasia to laparoscopic cardiomyotomy plus partial fundoplication. It was collected epidemiological data, specific diagnosis and subgroups, the presence or absence of gallstones, surgical procedure, operative and clinical complications and mortality. All groups/subgroups were compared. RESULTS: From 1,229 patients with GERD or esophageal achalasia, submitted to laparoscopic cardiomyotomy or fundoplication, 138 (11.43%) had cholelitiasis, occurring more in females (2.38:1) with mean age of 50,27 years old. In 604 patients with GERD, 79 (13,08%) had cholelitiasis. Lower prevalence occurred in Barrett's esophagus patients 7/105 (6.67%) (p=0.037). In 625 with esophageal achalasia, 59 (9.44%) had cholelitiasis, with no difference between chagasic and idiopathic forms (p=0.677). Complications of patients with or without cholecystectomy were similar in fundoplication and cardiomyotomy (p=0.78 and p=1.00).There was no mortality or complications related to cholecystectomy in this series. CONCLUSIONS: Prevalence of cholelithiasis was higher in patients submitted to fundoplication (GERD). Patients with chagasic or idiopatic ...

RACIONAL: São controversas as relações entre megaesôfago e doença do refluxo gastroesofágico (DRGE) com colelitíase, especialmente a forma mais adequada de conduzir pacientes com ambas. Dados epidemiológicos são díspares devido às diversas metodologias aplicadas, às diferenças regionais e à quantidade de pacientes envolvidos. OBJETIVO: Estudar a prevalência de colelitíase em pacientes submetidos às operações de refluxo gastroesofágico e megaesôfago (chagásicos ou não) e a segurança da colecistectomia estar associada. MÉTODO: Análise retrospectiva de 1410 pacientes operados entre 2000 e 2013. Eles foram divididos em dois grupos: os com DRGE e operados por hiatoplastia/fundoplicatura a Nissen laparoscópicas e os com acalásia por cardiomiotomia e fundoplicatura parcial laparoscópicas. Foram coletados dados epidemiológicos, diagnóstico, a presença ou não de litiase biliar, tratamento cirúrgico efetuado, complicações clínicas ou cirúrgicas e mortalidade. Todos os grupos e subgrupos foram comparados. RESULTADOS: Foram estudados 1229 pacientes portadores de megaesôfago e/ou DRGE, operados por fundoplicatura com hiatoplastia, nos casos de DRGE, e cardiomiectomia com fundoplicatura, nos casos de megaesôfago, no período de 2000 a 2013, verificando-se presença de colelítiase ou colecistectomia prévia. A colelítiase ocorreu mais no sexo feminino (2,38:1) e na faixa etária entre os 50 e 70 anos. A prevalência global foi de 11,43%; 13,08% na DRGE, menor nos portadores de esôfago de Barrett (6,67%) sendo a diferença significativa (p=0,037); e 9,44% no megaesôfago, não havendo diferença significativa entre os chagásicos e os idiopáticos (p=0,677). Não houve mortalidade ou complicações relacionadas à colecistectomia nesta série. CONCLUSÕES: A prevalência de colelitíase é maior nos pacientes com DRGE do que nos com megaesôfago. Não há diferenças na prevalência de colelitíase nos pacientes com megaesôfago chagásico e não chagásico. É mais frequente litíase ...