The effects of ACE2 expression mediating pharmacotherapy in COVID-19 patients.

BACKGROUND: There has been debate on the use of angiotensin-converting enzyme­2 (ACE2) expression mediating pharmacotherapy in COVID-19 infected patients. Although it has been suggested that these drugs might lead to a higher susceptibility and severity of COVID-19 infection, experimental data suggest these agents may reduce acute lung injury via blocking angiotensin-II-mediated pulmonary permeability, inflammation and fibrosis. METHODS: A systematic literature search was performed to answer the question: What is the effect of medications that influence ACE2 expression (ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), nonsteroidal anti-inflammatory drugs (NSAIDs) and thiazolidinediones) on the outcomes of COVID-19? Relevant outcome measures were mortality (crucial), hospital admission, length of stay, thromboembolic complications (pulmonary embolism, stroke, transient ischaemic attack), need for mechanical ventilation, acute kidney injury and use of renal replacement therapy. Medline and Embase databases were searched with relevant search terms until 24 June 2020. After systematic analysis, nine studies were included. RESULTS: The results were described for two different groups, an overall group in which all users were compared with non-users and a group in which only hypertensive patients were included. Within each group a distinction was made between results for ACEI/ARB use, ACEI use, ARB use, NSAID use and thiazolidinedione use. None of the studies demonstrated increased mortality in the two groups. Furthermore, none of the studies showed an effect on other outcome measures in COVID-19, such as ICU admission, length of hospital stay, thromboembolic complications, need for mechanical ventilation, acute kidney failure or need for renal replacement therapy. However, the level of evidence of all studies varied from 'moderate' to 'very low', according to the GRADE methodology. CONCLUSION: Analysis of the literature demonstrated that there was insufficient evidence to answer our objective on the effect of ACE2 expression mediating pharmacotherapy on outcome in COVID-19 patients, especially due to the low scientific quality of the described studies. Randomised controlled studies are needed to answer this question.

[Eduard Boeckmann--scientist, inventor and benefactor]. / Eduard Bøckmann--vitenskapsmann, oppfinner og velgjører.

Eduard Boeckmann (1849-1927) left a lasting legacy in Norway and in America. His scientific career started when as a medical student he won the Skjelderup gold medal for a study of the tonsils. In Bergen he presented his thesis, an experimental study dealing with the cause of keratitis, which affected many patients with leprosy. Later he published vigorously from his medical practice. In St. Paul, Minnesota, he constructed a steam autoclave based on principles that became fundamental in later autoclave technique. His autoclave was put into industrial production. In his own laboratory he worked with improvement and safe sterilization of catgut, and catgut was produced in St. Paul for 59 years, till 1960. He donated income from the catgut production to a fund for a medical library, today the Boeckmann Library of the United Hospital in St. Paul. Boeckmann had a high reputation as a doctor. His American patients were first of all Norwegian settlers in the north-western states. Both in Bergen and in St. Paul he was highly active in the professional associations.

[Eilert Støren, district medical officer in Meldalen]. / Distriktslaege Eilert Støren i Meldalen.

Eilert Støren (1860-1929) was the district medical officer in an inland community in mid-Norway for 40 years. He saw the medical problems in his area in a perspective beyond the patients' immediate needs. Based on his own observations he published four major medical works; two on tuberculosis, one on nutrition and one on lues. In addition he was the author of several singular publications on various topics, and some case reports. He was a pioneer in recording the cultural history of his community and produced more than 40 publications in this field. The local museum was founded on the basis of his collections of antiquities etc. He was also politically active and had a seat on the municipal council, and held several public commissions.

Prognostic importance of radical lymphadenectomy in curative resections for gastric cancer.

OBJECTIVE: To evaluate the effect of extensive lymphadenectomy on survival in patients with gastric cancer. DESIGN: Retrospective analysis SETTING: University Hospital, Norway. SUBJECTS: 183 patients with stomach cancer resected for cure during the time period 1980-90. INTERVENTIONS: 78 patients had an R1- and 105 patients and R2 resection. 124 patients were treated by total gastrectomy, 5 by proximal--and 54 by distal resection. MAIN OUTCOME MEASURES: Morbidity, mortality and long term survival. RESULTS: The morbidity was 33% (60/183), of which 39 (21%) were general complications (pneumonia, thrombosis, or cardiovascular disease). 14 patients died postoperatively (8%). By logistic regression analysis we found that splenectomy was the only variable associated with both morbidity and immediate postoperative mortality. Five year survival was 39% for patients who had undergone curative resections, 30% for patients who had had an R1 resection, and 47% for those who had had an R2 resection. By multivariate analysis (Cox) we found that N-classification (TNM), tumour diameter of less than 45 mm, type of lymph node dissection (R2) and operation period (after 1984) correlated with improved survival. CONCLUSION: Extensive lymph node dissection improves survival without increasing morbidity or postoperative mortality.

[Christian Wisbech--his hospital and surgery in the 1820s]. / Christian Wisbech--hans sykehus og kirurgi i 1820-årene.

Christian Wisbech (1801-1869) was medical superintendent of "Bergen civile Sygehus" during the period 1825-1848. Some of his annual reports have been published. The hospital had 56 beds. The permanent staff included one "spisemester" (caterer) and two "sygeopvartersker" (nurses). Christian Wisbech's medicine was based on strict scientific principles and pathological anatomy. A post-mortem was performed on the deceased. Other current trends in medical practice at that time were foreign to him. It is assumed that he was inspired by Giovanni Morgagni (1682-1771) and John Hunter (1728-1793). His treatment was partly medical and partly surgical. Wisbech treated surprisingly few injuries. A possible explanation is the large number of "barbers and surgeons" in Bergen at that time. It was probably a centuries-long tradition among the population to go to such persons to be treated for broken bones, wounds and other complaints.

The diagnostic potential of some routine laboratory tests. off.

The potential was tested of white blood cell count (WBC), haemoglobin concentration (Hb) and erythrocyte volume fraction (EVF) to differentiate between patients with acute mesenteric ischaemia (AMI), perforation of colon, perforation of peptic ulcer, and intestinal obstruction. The WBC in patients with AMI (18.95 +/- 6.88 10(3) ml-1) was significantly above the normal range (upper cut-off 11.0 10(3) ml-1; P < 0.0001). Other variables in the patient groups did not differ from those of healthy individuals. All variables were, however, different between patients with AMI and non-AMI (P < 0.001). Receiver operator characteristic (ROC) curves were constructed to define the optimal cut-off for each variable. Sensitivity and specificity of the variables were between 62% and 75%. Discriminant analysis of the variables classified 80% of the patients correctly into AMI and non-AMI groups.

Central venous catheter with subcutaneous injection port (Port-A-Cath): 8 years clinical follow up with children.

Long-term intermittent venous access was established in 77 children by means of a central venous catheter (CVC) with a subcutaneous injection port (Port-A-Cath; PAC). Seventy of these children were included in this follow-up study. Sixty-three were treated for different malignant diseases, five for cystic fibrosis, one for severe hemophilia and one for central nervous system disease with seizures as the main problem. As of April, 1992, PACs had been in place for 3/12 to 8 3/12 years (cumulative 175 5/12 years) with 2,206 entries into the system. The PACs were used for blood sampling and administration of chemotherapy, antibiotics, fluids, total parenteral nutrition (TPN) and blood products. Portal infection was observed in four patients of which two patients had their PAC removed. Catheter dislocation was observed in two and catheter breakage in one. Portal occlusion, extravasation, thrombosis leading to removal of the PAC or other technical or psychological complications were not observed. The children continued normal activities, and the easy venous access decreased emotional stress during treatment. Local doctors were trained to use PACs, through which they administered maintenance chemotherapy. We conclude that long-time use of PACs in children is safe and has many advantages compared to traditional CVCs in use. Strict indications, meticulous implantation techniques and adequate handling are, however, mandatory.

The influence of the host on the course of gastric carcinoma.

Immunoglobulins (Ig) and some complement components (C) were quantified in sera from patients with gastric carcinoma before surgery and at regular intervals during a 5-year follow-up. The preoperative concentrations of C1-INH and C4 were higher (P < 0.0005 and P < 0.005) and IgG lower (P < 0.0005) in 50 patients with recurrence than in 46 5-year survivors. The prognostic significant of C1-INH was superior to that of the extent of disease (F-values 37.1 and 26.1). The preoperative immune data classified 76% of the patients correctly as to recurrence and no recurrence. Also, the preoperative C1-INH concentration had a highly significant effect on time to recurrence of cancer (P = 0.0007), adjusting for age and disease extent. After surgery the mean IgG concentrations were within normal range and without difference between the two groups. On the other hand, the concentrations of C1-INH and C4 in the individual patients in both groups remained the same from before to after surgery and throughout the observation period (P = 0.34). Apparently, the serum levels of C1-INH and C4 do not reflect the bearing of cancer. We therefore suggest that these variables represent an independent immune state that is appropriate to the host. A comparison of our variables with those of healthy individuals seems to support this idea. This immune state has a significant influence on whether a resected gastric cancer will recur, and also on how soon recurrence may be manifest.

Long term results after Nissen fundoplication and Belsey Mark IV operation in patients with reflux oesophagitis and stricture.

This retrospective study was undertaken to compare long term results of Nissen fundoplication and the Belsey Mark IV repair in patients with reflux oesophagitis and stricture between 1972 and 1987. 105 patients were operated on for reflux oesophagitis, and 43 of the patients had stricture. There was one postoperative death (after a Belsey Mark IV repair). The cumulative recurrence rate after the Nissen operation was 9%, all recurrences of oesophagitis occurring within the first two years. The cumulative recurrence after the Belsey repair was 37%. Only 15 of 32 patients treated with Nissen fundoplication for stricture needed dilatation after operation, and then only during the first two years. "Gas-bloat" occurred in 18% of the patients treated with Nissen fundoplication. We conclude that the Nissen fundoplication is a good operation for patients with severe reflux oesophagitis and for those with peptic strictures of the oesophagus. The Belsey Mark IV repair, however, cannot be recommended for patients with strictures.

The influence of age on the growth and spread of gastric carcinoma.

A twelve year series of 375 patients with gastric carcinoma has been studied. Patients were divided into TNM Groups. Tumours were classified as intestinal-type and diffuse. The patients with T1-3NOMO diffuse tumour were ten years younger than the patients with T1-3NOMO intestinal-type tumour. The mean age increased from T1 through T2 to those with T3 tumour. The age differences between the T-stages were the same in both groups, which indicate that once started, the diffuse and the intestinal-type tumours infiltrate the gastric wall at about the same rate. Among the patients with intestinal-type tumour, those with lymph node or distant metastases were three to seven years younger than the patients without metastases. On the other hand, the patients with diffuse tumour and metastases were as many years older than the patients without metastases. Apparently, tumour spread is age dependent and different between the two types of gastric carcinoma. The ill repute of the diffuse gastric carcinoma may therefore be explained by the advanced stage of that tumour at the time of treatment as compared to the intestinal-type tumour. The diffuse tumour seems to be clinically more silent and to give symptoms at a later stage than the intestinal-type tumour.

Age and sex distribution of intestinal type and diffuse gastric carcinoma.

A twelve-year series of 375 patients with gastric carcinoma has been studied. Primary tumours were classified as intestinal type (58%) or diffuse (26%), whereas 16% were unclassifiable. The relative age and sex incidence rates of intestinal type and diffuse gastric carcinoma were estimated using the age and sex distribution of individuals in Norway as the basis for calculation. There was no difference in the rates of diffuse gastric carcinoma between the sexes. On the other hand, the rate of men with intestinal type carcinoma was more than twice as high as that of women. This difference was consistent within each age group from adolescence to senescence. The findings indicate that Laurén's two types of gastric carcinoma are aetiologically different. The rates of both types increased with age up to the 70-79 age group, whereas the rates in octogenarians tended to be lower than in septuagenarians. A comparison of our data with the data of incidence of gastric cancer in Norway indicates that some of the older patients do not come for surgery.

A simple on-line information system for quality assessment.

Many aspects of medicine would be well served by a simple method to assess the outcome of care in specified groups of patients. This study examined charts of patients with stomach cancer on a surgical service. Two digits were added to the ICD-9 number in the routine discharge data; one for the nature and severity of case and the other for the outcome of care. The digits were designed for on-line registration at discharge. Information was also obtained on resource consumption in the various groups of patients. Most of the variables had to be evaluated implicitly as there were no explicit judgement criteria and few empiric data available for comparison. Implicit evaluation of the results was significant and prompted steps for improving care. With current systems, the information obtained from traditional hospital statistics is limited and partly misleading. By slight modification, however, hospital statistics may provide valuable information for assessing quality of care and resource allocation during hospitalization.

Who gets a second primary cancer after gastric cancer surgery?

Eleven patients presented with a second primary cancer during follow-up after surgery for gastric carcinoma. In these patients the serum concentrations of C1-INH and IgG prior to gastric cancer surgery were similar to those of 53 patients with recurrence of gastric cancer. In these two groups, the preoperative C1-INH concentrations were higher and IgG lower (P less than 0.001 and P less than 0.05) when compared to 36 patients alive and disease-free 5 years after surgery. The median time between surgery and signs of recurrence was 11 months, whereas the median time until signs of the second primary cancer was 4 years. A patient with gastric carcinoma who pre-operatively has high C1-INH and low IgG is liable either to have recurrence or to develop a second primary cancer. Our data indicate that these variables represent a cancer susceptibility feature appropriate to the host.

Serum C1-esterase inhibitor, an essential and independent prognosticator of gastric carcinoma.

The preoperative concentrations of IgG were lower (P less than 0.002) and the concentrations of C4 and C1-INH higher (P less than 0.01 and P less than 0.001) in 29 patients with recurrence after potentially curative resection of gastric carcinoma, than in 31 patients alive and disease-free 5 years after surgery. These differences between the two groups of patients were consistent within each of six groups of disease extent. In each of the two groups of patients, the preoperative concentrations of IgG, C4 and C1-INH had no significant variation with the extent of disease (P greater than 0.05 or greater). Of our variables, C1-INH was the most potent prognosticator and discriminated between patients with and without recurrence with 80% accuracy. Furthermore, the predictive prognostic value of C1-INH at the time of surgery was superior to the prognostic value of the extent of disease (F values 27.00 and 12.69). Apparently, the preoperative C1-INH concentration is an essential and independent prognostic parameter of gastric carcinoma. We assume that C1-INH reflects an additional prognostic feature appropriate to the tumour or the host. Our finding that the interval between surgery and death from recurrence had an inverse relation to the preoperative C1-INH concentration also supports this assumption.

[Immune status in patients with acute gastrointestinal hemorrhage]. / Immunstatus hos pasienter med akutt blødning fra øvre gastrointestinaltractus.

The mortality rate after surgery for upper gastrointestinal bleeding is high, and cannot be explained by the blood loss as such, or by the operation itself. Our immune defence is suppressed by haemorrhagic shock, blood transfusion and surgery. The effect is cumulative, and in many of these patients the cause of death is a consequence of severe immune suppression. The suppressed immune state is brought about by mediators that are produced, released or impaired by various trauma. As of today, we cannot regulate our immune reactions in acute situations in an effective way. Accordingly, we must try to prevent the development of severe immune suppression. The first step in reducing the high mortality rate in patients with acute upper gastrointestinal bleeding is to identify, as soon as possible, persons who risk experiencing a second bleeding after the initial episode. Our present knowledge allows such identification with a rate of accuracy of approximately 70%-80%.