Systematic review and meta-analysis of endoscopic submucosal dissection versus transanal endoscopic microsurgery for large noninvasive rectal lesions

Background

For almost 30 years, transanal endoscopic microsurgery (TEM) has been the mainstay treatment for large rectal lesions. With the advent of endoscopic submucosal dissection (ESD), flexible endoscopy has aimed at en bloc R0 resection of superficial lesions of the digestive tract. This systematic review and meta-analysis compared the safety and effectiveness of ESD and full-thickness rectal wall excision by TEM in the treatment of large nonpedunculated rectal lesions preoperatively assessed as noninvasive.

Methods

A systematic review of the literature published between 1984 and 2010 was conducted (Registration no. CRD42012001882). Data were integrated with those from the original databases requested from the study authors when needed. Pooled estimates of the proportions of patients with en bloc R0 resection, complications, recurrence, and need for further treatment in the ESD and TEM series were compared using random-effects single-arm meta-analysis.

Results

This review included 11 ESD and 10 TEM series (2,077 patients). The en bloc resection rate was 87.8 % (95 % confidence interval [CI] 84.3–90.6) for the ESD patients versus 98.7 % (95 % CI 97.4–99.3 %) for the TEM patients (P < 0.001). The R0 resection rate was 74.6 % (95 % CI 70.4–78.4 %) for the ESD patients versus 88.5 % (95 % CI 85.9–90.6 %) for the TEM patients (P < 0.001). The postoperative complications rate was 8.0 % (95 %, CI 5.4–11.8 %) for the ESD patients versus 8.4 % (95 % CI 5.2–13.4 %) for the TEM patients (P = 0.874). The recurrence rate was 2.6 % (95 % CI 1.3–5.2 %) for the ESD patients versus 5.2 % (95 % CI 4.0–6.9 %) for the TEM patients (P < 0.001). Nevertheless, the rate for the overall need of further abdominal treatment, defined as any type of surgery performed through an abdominal access, including both complications and pathology indications, was 8.4 % (95 % CI 4.9–13.9 %) for the ESD patients versus 1.8 % (95 % CI 0.8–3.7 %) for the TEM patients (P < 0.001).

Conclusions

The ESD procedure appears to be a safe technique, but TEM achieves a higher R0 resection rate when performed in full-thickness fashion, significantly reducing the need for further abdominal treatment.     

Phosphate homeostasis in Bartter syndrome: a case–control study

Background

Bartter patients may be hypercalciuric. Additional abnormalities in the metabolism of calcium, phosphate, and calciotropic hormones have occasionally been reported.

Methods

The metabolism of calcium, phosphate, and calciotropic hormones was investigated in 15 patients with Bartter syndrome and 15 healthy subjects.

Results

Compared to the controls, Bartter patients had significantly reduced plasma phosphate {mean [interquartile range]:1.29 [1.16–1.46] vs. 1.61 [1.54–1.67] mmol/L} and maximal tubular phosphate reabsorption (1.16 [1.00–1.35] vs. 1.41 [1.37–1.47] mmol/L) and significantly increased parathyroid hormone (PTH) level (6.1 [4.5–7.7] vs. 2.8 [2.2–4.4] pmol/L). However, patients and controls did not differ in blood calcium, 25-hydroxyvitamin D, alkaline phosphatase, and osteocalcin levels. In patients, an inverse correlation (P?P?P?Conclusions The results of this study demonstrate a tendency towards renal phosphate wasting and elevated circulating PTH levels in Bartter patients.     

Electrolyte abnormalities in cystic fibrosis: systematic review of the literature

Background

Cystic fibrosis per se can sometimes lead to hyponatremia, hypokalemia, hypochloremia or hyperbicarbonatemia. This tendency was first documented 60 years ago and has subsequently been confirmed in single case reports or small case series, most of which were retrospective. However, this issue has not been addressed analytically. We have therefore systematically reviewed and analyzed the available literature on this subject.

Methods

This was a systematic review of the literature.

Results

The reports included in this review cover 172 subacute and 90 chronic cases of electrolyte imbalances in patients with cystic fibrosis. The male:female ratio was 1.57. Electrolyte abnormalities were mostly associated with clinically inapparent fluid volume depletion, mainly affected patients aged ≤2.5 years, frequently tended to recur and often were found before the diagnosis of cystic fibrosis was established. Subacute presentation often included an history of heat exposure, vomiting, excessive sweating and pulmonary infection. History of chronic presentation, in contrast, was often inconspicuous. The tendency to hypochloremia, hypokalemia and metabolic alkalosis was similar between subacute and chronic patients, with hyponatremia being more pronounced (P?<?0.02) in subacute compared to chronic presentations. Subacute cases were treated parenterally; chronic ones were usually managed with oral salt supplementation. Retention of urea and creatinine was documented in 38 % of subacute cases.

Conclusions

The findings of our review suggest that physicians should be aware that electrolyte abnormalities can occur both as a presenting and a recurring feature of cystic fibrosis.     

Detecting Maternal‐Fetal Genotype Interactions Associated With Conotruncal Heart Defects: A Haplotype‐Based Analysis With Penalized Logistic Regression

Nonsyndromic congenital heart defects (CHDs) develop during embryogenesis as a result of a complex interplay between environmental exposures, genetics, and epigenetic causes. Genetic factors associated with CHDs may be attributed to either independent effects of maternal or fetal genes, or the intergenerational interactions between maternal and fetal genes. Detecting gene‐by‐gene interactions underlying complex diseases is a major challenge in genetic research. Detecting maternal‐fetal genotype (MFG) interactions and differentiating them from the maternal/fetal main effects has presented additional statistical challenges due to correlations between maternal and fetal genomes. Traditionally, genetic variants are tested separately for maternal/fetal main effects and MFG interactions on a single‐locus basis. We conducted a haplotype‐based analysis with a penalized logistic regression framework to dissect the genetic effect associated with the development of nonsyndromic conotruncal heart defects (CTD). Our method allows simultaneous model selection and effect estimation, providing a unified framework to differentiate maternal/fetal main effect from the MFG interaction effect. In addition, the method is able to test multiple highly linked SNPs simultaneously with a configuration of haplotypes, which reduces the data dimensionality and the burden of multiple testing. By analyzing a dataset from the National Birth Defects Prevention Study (NBDPS), we identified seven genes (GSTA1, SOD2, MTRR, AHCYL2, GCLC, GSTM3, and RFC1) associated with the development of CTDs. Our findings suggest that MFG interactions between haplotypes in three of seven genes, GCLC, GSTM3, and RFC1, are associated with nonsyndromic conotruncal heart defects.     

Educational and Organizational Interventions to Improve the Usefulness of Clinical Pharmacological Advice for Personalized Drug Dosing Based on Therapeutic Drug Monitoring

This study was aimed at increasing the clinical usefulness of clinical pharmacological advice (CPA) for personalized drug dosing based on therapeutic drug monitoring (TDM). Educational and organizational interventions focused on improving the knowledge of clinical pharmacology among hospital healthcare workers and reducing the incidence of errors throughout the process were planned. After a pre‐interventional period of risk assessment, different list forms of the types of error occurring in the various phases of the process (Phase 1, request for CPA and blood sampling for TDM; Phase 2, sample delivery to and check in at the CPU; Phase 3, TDM execution and CPA production) were created. In the interventional period, the errors were collected daily and educational programmes were carried out. The pre‐intervention error rate was 19.5%, and resulted significantly higher for the requests coming from the medical wards compared with those from the surgical wards or the ICUs (26.0% versus 10.5% versus 13.7%, p < 0.001). The educational programme trained 303 nurses and 145 physicians. Afterwards, the error percentage progressively dropped (15.5% in the 2nd trimester; 12.3% in the 3rd one; 10.5% in the 4th one). The adopted strategy resulted in significant improvements which may be useful both to improve quality of patient care and to reduce waste in healthcare costs.     

Synthesis,in Vitro Covalent Binding Evaluation,and Metabolism of 14C-Labeled Inhibitors of 11β-HSD1

相似文献   

A view from the other side: the hope in the eyes of the healer

A physician affected by amyotrophic lateral sclerosis (ALS) explores the meaning of his disease. The deterioration of his physical health and of his independence provided a new and deeper view of healing, as well as a new mission for his medical profession. He has become at the same time a “voice for the voiceless” and a source of hope and inspiration for patients and health professionals alike. Espousing the principle that healing is always possible even when the disease is incurable, the author proposes a three-prong approach to healing: symptom management, allegiance to the patient up to the ends, and common search of meaning. He emphasizes that both patients and health care workers need to be healed.     

Expansion of plasmablasts and loss of memory B cells in peripheral blood from COVID-19 patients with pneumonia

Studies on the interactions between SARS-CoV-2 and humoral immunity are fundamental to elaborate effective therapies including vaccines. We used polychromatic flow cytometry, coupled with unsupervised data analysis and principal component analysis (PCA), to interrogate B cells in untreated patients with COVID-19 pneumonia. COVID-19 patients displayed normal plasma levels of the main immunoglobulin classes, of antibodies against common antigens or against antigens present in common vaccines. However, we found a decreased number of total and naïve B cells, along with decreased percentages and numbers of memory switched and unswitched B cells. On the contrary, IgM⁺ and IgM⁻ plasmablasts were significantly increased. In vitro cell activation revealed that B lymphocytes showed a normal proliferation index and number of dividing cells per cycle. PCA indicated that B-cell number, naive and memory B cells but not plasmablasts clustered with patients who were discharged, while plasma IgM level, C-reactive protein, D-dimer, and SOFA score with those who died. In patients with pneumonia, the derangement of the B-cell compartment could be one of the causes of the immunological failure to control SARS-Cov2, have a relevant influence on several pathways, organs and systems, and must be considered to develop vaccine strategies.     

It's costly punishment,not altruistic: Low midfrontal theta and state anger predict punishment

Punishment in economic games has been interpreted as “altruistic.” However, it was shown that punishment is related to trait anger instead of trait altruism in a third-party dictator game if compensation is also available. Here, we investigated the influence of state anger on punishment and compensation in the third-party dictator game. Therefore, we used movie sequences for emotional priming, including the target states anger, happy, and neutral. We measured the Feedback-Related Negativity (FRN) and midfrontal theta band activation, to investigate an electro-cortical correlate of the processing of fair and unfair offers. Also, we assessed single-trial FRN and midfrontal theta band activation as a predictor for punishment and compensation. We found that punishment was linked to state anger. Midfrontal theta band activation, which has previously been linked to altruistic acts and cognitive control, predicted less punishment. Additionally, trait anger led to enhanced FRN for unfair offers. This led to the interpretation that the FRN depicts the evaluation of fairness, while midfrontal theta band activation captures an aspect of cognitive control and altruistic motivation. We conclude that we need to redefine “altruistic punishment” into “costly punishment,” as no direct link of altruism and punishment is given. Additionally, midfrontal theta band activation complements the FRN and offers additional insights into complex responses and decision processes, especially as a single trial predictor.