Refractory Thrombocytopenia Responds to Octreotide Treatment in a Case of Evans Syndrome with Gastric Neuroendocrine Tumor

A 37-year-old woman with history of Evans Syndrome with poor response to high-dose corticoid treatment presented to the emergency department with gastrointestinal and vaginal bleeding. The patient was later diagnosed with severe thrombocytopenia and a stage G1, well-differentiated gastric neuroendocrine tumor, confirmed by a biopsy. A total gastrectomy was performed to eradicate the tumor. After being treated with a total splenectomy for her Evans Syndrome with no clinical or laboratory improvement, she began regular treatment with octreotide on the basis of a possible hepatic metastasis. Days after the initiation of the octreotide, an increase in the platelet count was evidenced by laboratory findings, from 2,000 platelets/mm3 to 109,000 platelets/mm3 . Weeks later, the hepatic metastasis is discarded by a negative octreotide-body scan, and the octreotide treatment was interrupted. Immediately after the drug interruption, a progressive and evident descent in the platelet count was evidenced (4000 platelets/mm3 ). The present case report highlights the possible association between octreotide treatment and a severe thrombocytopenia resistant to conventional treatment.Revisión por pare

The Color of Noise and Weak Stationarity at the NREM to REM Sleep Transition in Mild Cognitive Impaired Subjects

In Older Adults (OAs), Electroencephalogram (EEG) slowing in frontal lobes and a diminished muscle atonia during Rapid Eye Movement sleep (REM) have each been effective tracers of Mild Cognitive Impairment (MCI), but this relationship remains to be explored by non-linear analysis. Likewise, data provided by EEG, EMG (Electromyogram) and EOG (Electrooculogram)—the three required sleep indicators—during the transition from REM to Non-REM (NREM) sleep have not been related jointly to MCI. Therefore, the main aim of the study was to explore, with results for Detrended Fluctuation Analysis (DFA) and multichannel DFA (mDFA), the Color of Noise (CN) at the NREM to REM transition in OAs with MCI vs. subjects with good performances. The comparisons for the transition from NREM to REM were made for each group at each cerebral area, taking bilateral derivations to evaluate interhemispheric coupling and anteroposterior and posterior networks. In addition, stationarity analysis was carried out to explore if the three markers distinguished between the groups. Neuropsi and the Mini-Mental State Examination (MMSE) were administered, as well as other geriatric tests. One night polysomnography was applied to 6 OAs with MCI (68.1 ± 3) and to 7 subjects without it (CTRL) (64.5 ± 9), and pre-REM and REM epochs were analyzed for each subject. Lower scores for attention, memory and executive funcions and a greater index of arousals during sleep were found for the MCI group. Results confirmed that EOGs constituted significant markers of MCI, increasing the CN for the MCI group in REM sleep. The CN of the EEG from the pre-REM to REM was higher for the MCI group vs. the opposite for the CTRL group at frontotemporal areas. Frontopolar interhemispheric scaling values also followed this trend as well as right anteroposterior networks. EMG Hurst values for both groups were lower than those for EEG and EOG. Stationarity analyses showed differences between stages in frontal areas and right and left EOGs for both groups. These results may demonstrate the breakdown of fractality of areas especially involved in executive functioning and the way weak stationarity analyses may help to distinguish between sleep stages in OAs

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Refractory Thrombocytopenia Responds to Octreotide Treatment in a Case of Evans Syndrome with Gastric Neuroendocrine Tumor

A 37-year-old woman with history of Evans Syndrome with poor response to high-dose corticoid treatment presented to the emergency department with gastrointestinal and vaginal bleeding. The patient was later diagnosed with severe thrombocytopenia and a stage G1, well-differentiated gastric neuroendocrine tumor, confirmed by a biopsy. A total gastrectomy was performed to eradicate the tumor. After being treated with a total splenectomy for her Evans Syndrome with no clinical or laboratory improvement, she began regular treatment with octreotide on the basis of a possible hepatic metastasis. Days after the initiation of the octreotide, an increase in the platelet count was evidenced by laboratory findings, from 2,000 platelets/mm(3) to 109,000 platelets/mm(3). Weeks later, the hepatic metastasis is discarded by a negative octreotide-body scan, and the octreotide treatment was interrupted. Immediately after the drug interruption, a progressive and evident descent in the platelet count was evidenced (4000 platelets/mm(3)). The present case report highlights the possible association between octreotide treatment and a severe thrombocytopenia resistant to conventional treatment

Table_1_The Color of Noise and Weak Stationarity at the NREM to REM Sleep Transition in Mild Cognitive Impaired Subjects.pdf

<p>In Older Adults (OAs), Electroencephalogram (EEG) slowing in frontal lobes and a diminished muscle atonia during Rapid Eye Movement sleep (REM) have each been effective tracers of Mild Cognitive Impairment (MCI), but this relationship remains to be explored by non-linear analysis. Likewise, data provided by EEG, EMG (Electromyogram) and EOG (Electrooculogram)—the three required sleep indicators—during the transition from REM to Non-REM (NREM) sleep have not been related jointly to MCI. Therefore, the main aim of the study was to explore, with results for Detrended Fluctuation Analysis (DFA) and multichannel DFA (mDFA), the Color of Noise (CN) at the NREM to REM transition in OAs with MCI vs. subjects with good performances. The comparisons for the transition from NREM to REM were made for each group at each cerebral area, taking bilateral derivations to evaluate interhemispheric coupling and anteroposterior and posterior networks. In addition, stationarity analysis was carried out to explore if the three markers distinguished between the groups. Neuropsi and the Mini-Mental State Examination (MMSE) were administered, as well as other geriatric tests. One night polysomnography was applied to 6 OAs with MCI (68.1 ± 3) and to 7 subjects without it (CTRL) (64.5 ± 9), and pre-REM and REM epochs were analyzed for each subject. Lower scores for attention, memory and executive funcions and a greater index of arousals during sleep were found for the MCI group. Results confirmed that EOGs constituted significant markers of MCI, increasing the CN for the MCI group in REM sleep. The CN of the EEG from the pre-REM to REM was higher for the MCI group vs. the opposite for the CTRL group at frontotemporal areas. Frontopolar interhemispheric scaling values also followed this trend as well as right anteroposterior networks. EMG Hurst values for both groups were lower than those for EEG and EOG. Stationarity analyses showed differences between stages in frontal areas and right and left EOGs for both groups. These results may demonstrate the breakdown of fractality of areas especially involved in executive functioning and the way weak stationarity analyses may help to distinguish between sleep stages in OAs.</p

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health