Factors associated with clinically significant hypoglycemia in patients with type 1 diabetes using sensor-augmented pump therapy with predictive low-glucose management: A multicentric study on iberoamerica

Background and aimsDespite using sensor-augmented pump therapy (SAPT) with predictive low-glucose management (PLGM), hypoglycemia is still an issue in patients with type 1 Diabetes (T1D). Our aim was to determine factors associated with clinically significant hypoglycemia (<54 mg/dl) in persons with T1D treated with PLGM-SAPT.Methodology: This is a multicentric prospective real-life study performed in Colombia, Chile and Spain. Patients with T1D treated with PLGM-SAPT, using sensor ≥70% of time, were included. Data regarding pump and sensor use patterns and carbohydrate intake from 28 consecutive days were collected. A bivariate and multivariate Poisson regression analysis was carried out, to evaluate the association between the number of events of <54 mg/dl with the clinical variables and patterns of sensor and pump use.Results188 subjects were included (41 ± 13.8 years-old, 23 ± 12 years disease duration, A1c 7.2% ± 0.9). The median of events <54 mg/dl was four events/patient/month (IQR 1–10), 77% of these events occurred during day time. Multivariate analysis showed that the number of events of hypoglycemia were higher in patients with previous severe hypoglycemia (IRR1.38; 95% CI 1.19–1.61; p < 0.001), high glycemic variability defined as Coefficient of Variation (CV%) > 36% (IRR 2.09; 95%CI 1.79–2.45; p < 0.001) and hypoglycemia unawareness. A protector effect was identified for adequate sensor calibration (IRR 0.77; 95%CI 0.66–0.90; p:0.001), and the use of bolus wizard >60% (IRR 0.74; 95%CI 0.58–0.95; p:0.017).ConclusionIn spite of using advanced SAPT, clinically significant hypoglycemia is still a non-negligible risk. Only the identification and intervention of modifiable factors could help to prevent and reduce hypoglycemia in clinical practice.     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma

Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings.     

Primary glioblastomas and anaplastic astrocytoma in a glioma family.

A 72-year-old man presented with a short duration of symptoms relating to a right fronto-parietal glioblastoma and a family history of children with brain tumours. Analysis of the patient's family tree revealed that out of seven children, he had a living son with anaplastic astrocytoma, a daughter who had died with a glioblastoma, and a son who had died with a histologically undiagnosed intrinsic brain tumour. One niece was also thought to have died from a brain tumour. All of the other affected family members had onset in their third or fourth decades. Tissue was only available from two of the affected individuals, precluding familial genetic analysis at this stage. There is no clinical evidence to support a diagnosis of a multiple cancer or neurocutaneous syndrome in this family. In view of what is known about the genetics of familial glioma, it is interesting to note the clinical evidence of both 'primary' glioblastoma and anaplastic astrocytoma in the same kindred.     

The everyday realities of the multi-dimensional role of the high school community nurse.

The traditional role of the high school based community community health nurse has changed considerably over recent decades. This article describes a qualitative study, in which nine community health nurses from eight different high schools completed a diary of the interventions and events during the course of two working days in order to identify the dimensions of their role. A short demographic questionnaire was also completed by the nurses and included two open-ended questions concerning their main professional issues and concerns. The researchers sought verification of the interpretation of the data through a focus group interview with the high school nurses. Data analysis indicated that the role of the high school community health nurses (CHN) consisted of seven categories. These were provider of clinical care, counsellor/ mediator, advocacy and support, liaison/referral, health promotion/education and resource agent, and professional management and research role. The findings highlight the complex and demanding aspects of the role of the high school nurse and articulate the importance of describing the contribution of such practitioners in to the promotion of health among adolescents.     

Deep Granuloma Annulare (Pseudorheumatoid Nodule) in Children: Clinicopathologic Study of 35 Cases

Deep granuloma annulare (DGA) is one of several lesions of skin and superficial soft tissues whose histologic character is a palisading granuloma with a small central focus of necrosis or necrobiosis. Unlike the other palisading necrobiotic lesions, DGA has a predilection for children in the first 5 to 6 years of life. A painless subcutaneous nodule(s) in the lower anterior tibial region or foot and the scalp, typically in the occiput, was the most common presenting feature in this study of 35 cases. Additional or recurrent lesions were reported in approximately 70% of cases with clinical follow-up. All lesions showed the presence of necrobiosis; however, one of the characteristic features was the multinodular character of the predominantly mononuclear cellular aggregates. The presence of vascular spaces at the periphery of the nodular profiles served as a clue to the diagnosis of DGA. The palisading arrangement of the mononuclear cells was evident only in those foci with central necrobiosis. A histiocytic disorder or fibrohistiocytic process was a common consideration in the differential diagnosis, especially in those cases with less apparent foci of necrosis. Palisading histiocytes with prominent eosinophilic cytoplasm and some nuclear atypism were problematic with regard to possible epithelioid sarcoma. Our study failed to identify any underlying or predisposing factors in the development of DGA. Despite the fact that DGA is a well-documented lesion in children, it occurs sufficiently infrequently that it is often not considered clinically when it presents as a subcutaneous mass or masses in a child. Its recognition by the pathologist is especially important as the occurrence of additional lesions in a high proportion of children can be anticipated without undue concern. Received June 16, 1997; accepted October 28, 1997.     

Ninety-Six Five-Year Survivors After Liver Resection for Metastatic Colorectal Cancer

Background: Studies have consistently confirmed the benefit of liver resection for metastatic colorectal cancer. Few reports, however, have a long enough followup or sufficient 5-year survivors to study the clinical course of patients beyond 5 years.

Study Design: From July 1985 through December 1991, 456 patients underwent liver resection for colorectal metastases. Ninety-six actual 5-year survivors (21%) were identified and their clinical course retrospectively reviewed.

Results: Five-year survivors (n = 96) were more likely to have a Duke’s B primary colorectal carcinoma, fewer than four metastatic lesions, unilobar disease, and a negative histologic margin when compared with patients not surviving 5 years (n = 298). Forty-four (46%) of the 96 five-year survivors had a recurrence after hepatectomy. Of these 44, 19 (43%) were rendered disease free after further treatment. Overall, 71 of the 96 five-year survivors were free of disease at last followup. The actuarial 10-year survival of this group was 78%.

Conclusions: Patients that are disease free 5 years after liver resection are likely to have been cured by liver resection. Patients should be aggressively followed for recurrence because of the potential for further treatment and longterm survival.     

Changes in zinc level in the serum, whole blood and erythrocytes in disorders of thyroid function

The zinc level in serum and whole blood was determined in a series of 121 patients, 20 suffering from overt hyperthyroidism, 34 with manifest hypothyroidism and a control group of 67 euthyroid subjects. The zinc content per deciliter of erythrocytes was calculated from the haematocrit. The hyperthyroid group revealed a highly significantly elevated serum zinc level (p less than 0.01), but a most significantly reduced zinc content in whole blood (p less than 0.001) in comparison with the euthyroid group. On the other hand, the reverse changes were observed in the hypothyroid group, i.e. a most significantly reduced serum zinc content (p less than 0.001) and a highly significantly increased zinc content in whole blood (p less than 0.01). These results suggest that the determination of zinc levels both in serum and in whole blood may be a useful additional parameter of peripheral thyroid hormone effect.