Reintervention or mortality within 90 days of bariatric surgery: population-based cohort study.

BACKGROUND: Bariatric surgery carries a risk of severe postoperative complications, sometimes leading to reinterventions or even death. The incidence and risk factors for reintervention and death within 90 days after bariatric surgery are unclear, and were examined in this study. METHODS: This population-based cohort study included all patients who underwent bariatric surgery in one of the five Nordic countries between 1980 and 2012. Data on surgical and endoscopic procedures, diagnoses and mortality were retrieved from national high-quality and complete registries. Multivariable Cox regression analysis was used to calculate hazard ratios (HRs), adjusted for country, age, sex, co-morbidity, type of surgery and approach, year and hospital volume of bariatric surgery. RESULTS: Of 49 977 patients, 1111 (2·2 per cent) had a reintervention and 95 (0·2 per cent) died within 90 days of bariatric surgery. Risk factors for the composite outcome reintervention/mortality were older age (HR 1·65, 95 per cent c.i. 1·36 to 2·01, for age at least 50 years versus less than 30 years) and co-morbidity (HR 2·66, 1·53 to 4·62, for Charlson co-morbidity index score 2 or more versus 0). The risk of reintervention/mortality was decreased for vertical banded gastroplasty compared with gastric bypass (HR 0·37, 0·28 to 0·48) and more recent surgery (HR 0·51, 0·39 to 0·67, for procedures undertaken in 2010 or later versus before 2000). Sex, surgical approach (laparoscopic versus open) and hospital volume did not influence risk of reintervention/mortality, but laparoscopic surgery was associated with a lower risk of 90-day mortality (HR 0·29, 0·16 to 0·53). CONCLUSION: Reintervention and death were uncommon events within 90 days of bariatric surgery even in this unselected nationwide cohort from five countries. Older patients with co-morbidities have an increased relative risk of these outcomes.

ANTECEDENTES: La cirugía bariátrica conlleva un riesgo de complicaciones postoperatorias graves, que algunas veces ocasionan reintervenciones o incluso son causa de mortalidad. La incidencia y los factores de riesgo de reinterveniones y mortalidad a los 90 días tras cirugía bariátrica no están claros, y fueron examinados en este estudio. MÉTODOS: Todos los pacientes que fueron sometidos a cirugía bariátrica en uno de los cinco países nórdicos en 1980-2012 fueron incluidos en un estudio de cohortes de base poblacional. Los datos de los procedimientos quirúrgicos y endoscópicos, diagnóstico, y mortalidad se obtuvieron a partir de registros nacionales completos y de alta calidad. Mediante una regresión de Cox multivariable se obtuvieron los cocientes de riesgos instantáneos (hazard ratios, HR) y los intervalos de confianza 95% (i.c. del 95%) ajustados por país, edad, sexo, comorbilidad, y tipo, abordaje, año y volumen de casos de cirugía bariátrica del hospital. RESULTADOS: De un total de 49.977 pacientes, 1.111 (2,2%) precisaron una reintervención y 95 (0,2%) fallecieron durante los primeros 90 días tras la cirugía bariátrica. Los factores de riesgo para el resultado compuesto reintervención/mortalidad fueron la edad avanzada (HR = 1,7 (i.c. del 95% 1,4-2,0) edad ≥ 50 versus < 30 años)) y la comorbilidad (HR = 2,7 (i.c. del 95% 1,5-4,6) puntuación del índice de comorbilidad de Charlson ≥ 2 versus 0)). Se observó una disminución de los HRs tras la gastroplastia vertical con banda en comparación con el bypass gástrico (HR = 0,4, (i.c. del 95% 0,3-0,5)) y el periodo de estudio más reciente (HR = 0,5 (i.c. del 95% 0,4-0,7) ≥ 2010 versus < 2000)). El sexo, el abordaje quirúrgico laparoscópico versus abierto y el volumen del hospital no influyeron sobre el riesgo de reintervención/mortalidad, pero la cirugía laparoscópica se asoció con una mortalidad a los 90 días más baja (HR 0,3, i.c. del 95% 0,2-0,5). CONCLUSIÓN: La reintervención y la mortalidad son eventos infrecuentes durante los primeros 90 días tras la cirugía bariátrica, incluso en esta cohorte nacional y no seleccionada de cinco paises. Los pacientes mayores con comorbilidades tienen un riesgo relativo aumentado de reintervención y mortalidad.

How Well Planned Urgency Class Come True in The Emergency Surgery? Timing of Acute Care Surgery.

BACKGROUND AND AIMS: Emergency surgery represents an essential aspect of surgical care, but little is known about realization of the planned emergency class. Different systems such as NCEPOD classification and Timing of Acute Care Surgery classification have been developed for the timing of the emergency surgery. The aim of the study was to find out how well planned urgency class is being implemented. MATERIALS AND METHODS: The planned and realized waiting times for all emergency surgeries were studied during the 6-month period in the Oulu University Hospital. The catchment area of the hospital includes a population of 742,000. The urgency in the hospital is planned in a four-step scale: an extremely urgent (E) patient should be taken immediately to the operating theater. Class I urgency surgery should start within 3 h (180 min), class II within 8 h (480 min), and class III within 24 h (1440 min). Surgeon plans urgency at his discretion, and no specific urgency has been imposed on certain diagnoses thus the surgeon's perceptions of the illness or trauma affects the assessment. RESULTS: Extreme urgent patients had an average waiting time of 26 min. For class I patient, the average waiting time was 59 min, while 93% of surgeries were started within the target time. For class II and class III patients, these figures were 337 min and 86% and 830 min and 78%, respectively. CONCLUSION: With regard to urgency, the higher the degree of urgency, the greater the chance of the surgery being realized within the planned time.

Blister fluid and serum cytokine levels in severe sepsis in humans reflect skin dysfunction.

BACKGROUND: Knowledge of sepsis-related end-organ inflammation in vivo is limited. We investigated the cytokine response in skin and in serum in sepsis and its relation to multiorgan failure (MOF) and survival. METHODS: Cytokines were analysed in serum and in suction blister fluid of intact skin of 44 patients with severe sepsis and 15 healthy controls. Blister fluid and serum samples were collected within 48 h of the first sepsis-induced organ failure. This is a substudy of a larger follow-up study on wound healing in sepsis. RESULTS: Cytokine levels were higher in patients with sepsis vs. controls (interleukin [IL]-10, blisters: 65.9 vs. 4.3 pg/ml, P < 0.001, serum: 25.7 vs. 4.5 pg/ml, P = 0.004; IL-6, blisters: 41.9 vs. 0.03 pg/ml, P < 0.001, serum: 45.5 vs. 2.1 pg/ml, P < 0.001). Patients with MOF had higher levels of IL-10 (116.4 vs. 21.3 pg/ml, P = 0.015), IL-4 (0.7 vs. 0.07 pg/ml, P = 0.013) and basic fibroblast growth factor (bFGF) (25.9 vs. 9.5 pg/ml, P = 0.027) in blister fluid than patients without MOF. In blister fluid, survivors had lower levels of IL-10 (43.3 vs. 181.9 pg/ml, P = 0.024) and bFGF (15.8 vs. 31.9 pg/ml, P = 0.006) than non-survivors. In serum, survivors had higher levels of vascular endothelial growth factor (VEGF) (152.2 vs. 14.7 pg/ml, P = 0.012) and lower levels of IL-6 (38.5 vs. 91.1 pg/ml, P = 0.011) than non-survivors. The blister fluid levels of bFGF, TNF and VEGF did not correlate with the serum levels. CONCLUSIONS: Cytokine responses in skin blister fluid in patients with sepsis differed from those in healthy controls.

Dermal expression of laminin-332 and type IV collagen in humans with severe sepsis.

BACKGROUND: An intact basement membrane at the dermal-epidermal junction is essential to the viability of the skin. The effect of sepsis on the basement membrane is unknown. METHODS: Skin biopsies were used to study basement membrane structure in severe sepsis (Day 1). Subsequent biopsies were taken on Day 8 and at 3 months in the survivors. Immunohistochemical staining was undertaken using laminin-223 and type IV collagen. Twenty patients with severe sepsis and four control subjects were included in the analysis. RESULTS: Intensive care unit mortality was 4/20, and total 30-day mortality was 5/20. Exactly, 7/17 of patients with severe sepsis exhibited weak or absent laminin-332 expression and 11/15 exhibited weak or absent type IV collagen expression compared with 0/4 of control subjects on Day 1 in intact skin. The proportion of sepsis patients with weak or absent laminin-332 expression was 5/11 on Day 8 and fell to 1/7 at 3 months. The proportion of sepsis patients with weak or absent type IV collagen expression was 10/11 on Day 8 and 4/7 at 3 months. CONCLUSION: These findings suggest that basement membrane formation may be compromised in patients with severe sepsis.

Treatment of esophageal perforation in octogenarians: a multicenter study.

Esophageal perforation is associated with significant mortality, and this may markedly increase with advanced age. This multicenter study investigates this issue in patients older than 80 years. Data on 33 patients >80 years old who underwent conservative (10 patients), endoclip (one patient), stent grafting (11 patients), or surgical treatment (11 patients) for esophageal perforation were collected from nine centers. Surgical repair consisted of repair on drain in one patient, primary repair in seven patients, and esophagectomy in two patients. Among patients who underwent stent grafting, one required repeat stenting and another stent graft repositioning. One patient was converted to surgical repair after stent grafting. Thirteen patients (39.4%) died during the 30-day and/or in-hospital stay. Their mortality was significantly higher than in a series of patients<80 years old (13.0%, 21/161 patients, P=0.001). Three patients (30.0%) died after conservative treatment, one (100%) after treatment with endoclips, five (45.5%) after stent grafting, and four (36.4%) after surgical repair (P=0.548). Early survival with salvaged esophagus was 42.4% (conservative treatment: 70.0% endoclips 0%, stent grafting: 54.5%, and surgical repair: 54.5%, respectively, P=0.558). Estimated glomerular filtration rate<60 mL/minute/1.73 m2 (70.0% vs. 25.0%, P=0.043) and sepsis (100% vs. 32.1%, P=0.049) at presentation were associated with increased risk of early mortality in univariate analysis. Esophageal perforation in octogenarians is associated with very high early and intermediate high mortality irrespective of the treatment method used.

Cost-utility of bariatric surgery for morbid obesity in Finland.

BACKGROUND: The aim of this study was to evaluate the cost-utility of bariatric surgery (gastric bypass, sleeve gastrectomy and gastric banding) compared with ordinary treatment in the Finnish healthcare system. METHODS: Analysis was done from a healthcare provider's perspective using a combination of a decision tree and a Markov model, with a time horizon of 10 years. Health-related quality of life was estimated from a representative population survey, and other parameter values were based on registers, systematic reviews, controlled studies and expert opinion. RESULTS: In the base-case analysis, bariatric surgery was both more effective and less costly than the ordinary treatment. The mean costs were €33,870 and €50,495, and the mean number of quality-adjusted life-years 7·63 and 7·05, for bariatric surgery and ordinary treatment respectively. Uncertainty around the parameter values was tested comprehensively in sensitivity analyses, and the results were robust. CONCLUSION: Surgery for morbid obesity increases health-related quality of life, and reduces the need for further treatments and total healthcare costs. According to this analysis, non-operative care would be more costly for the Finnish healthcare system on average after 5 years following surgery.

Continuous retention suture for the management of open abdomen: a high rate of delayed fascial closure.

BACKGROUND AND AIMS: Open abdomen is most often a consequence of damage control surgery, abdominal decompression or intra-abdominal infections. Ventral hernia after unsuccessful closure of open abdomen causes marked disability to the patient. Several methods for delayed fascial closure have been developed. Patients treated with continuous retention suture were evaluated to find out how often fascial closure was achieved, and what complications were related to the technique. METHOD: A retrospective analysis of 16 open abdomen patients treated with continuous retention suture. RESULTS: The most common cause of open abdomen was abdominal infection. Complete fascial closure was achieved in nine of the eleven surviving patients. Closure failed in one patient. Partial closure was also achieved in one patient. The median time between leaving the abdomen open and starting the process of closure was twelve days. The longest period of open abdomen before successful fascial closure was 29 days. Five patients died before the process of closure was complete. CONCLUSION: Delayed fascial closure can be accomplished by using the retention suture method described here.

Organ system dysfunction following open cholecystectomy for acute acalculous cholecystitis in critically ill patients.

BACKGROUND: Acute acalculous cholecystitis (AAC) refers to cholecystitis without gallstones and is a serious complication of critical illness. We describe the time course of organ system dysfunction associated with cholecystectomy in critically ill patients with AAC. METHODS: The data of all intensive care unit (ICU) patients who had operatively confirmed AAC during their ICU stay between 2003 and 2004 were analyzed. Patients who also had other intra-abdominal pathologies were excluded. The Sequential Organ Failure Assessment (SOFA) scores were recorded 3 days before, on the day of operation and on the first, second, third and seventh post-operative day after cholecystectomy. The impact of open cholecystectomy on organ dysfunction was evaluated on the basis of the change in the total and individual organ SOFA scores. RESULTS: Twenty-four patients underwent open cholecystectomy for AAC with no other intra-abdominal pathology. Sepsis was the most common admission diagnosis, followed by cardiovascular surgery. The mean (standard deviation, SD) Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS) II and SOFA scores on admission were 24.7 (5.8), 44.3 (12.3) and 9.4 (3.2), respectively. The median (25th, 75th percentiles) total SOFA score 3 days before cholecystectomy was 7.5 (1.3, 8.0), which increased to 10.5 (8.3, 13.0) (P < 0.0001) by the day of cholecystectomy, indicating developing multiorgan dysfunction. After the operation, the score decreased to 5.5 (3.3, 10.8) (P = 0.004) by the seventh post-operative day. The change was most obvious in cardiovascular and respiratory SOFA scores. CONCLUSIONS: AAC is associated with multiorgan dysfunction in critically ill patients. Open cholecystectomy seems to alter the course of multiorgan dysfunction in these patients.

Staged endovascular stent-grafting and surgical treatment of a secondary aortoduodenal fistula.

Secondary aortoenteric fistula is a dramatic, rather infrequent late complication occurring mostly after abdominal aortic surgery. Currently, graft excision and in situ bypass is considered the treatment of choice, but it is associated with significant mortality and morbidity. Herein, we describe the case of a secondary aortoduodenal fistula treated by staged endovascular stent-grafting and surgical closure of the fistula. Forty days after stent-grafting, Tc-99m-HMPAO labelled leukocyte scanning failed to identify leukocyte infiltration of the graft and there were no clinical signs of infection. At 8-month follow up, the patient was asymptomatic.

Histopathology of acute acalculous cholecystitis in critically ill patients.

AIMS: To illustrate the histopathological features of acute acalculous cholecystitis (AAC) of critically ill patients and to compare them with those of acute calculous cholecystitis (ACC) and normal gallbladders. METHODS AND RESULTS: We studied 34 gallbladders with AAC and compared them with 28 cases of ACC and 14 normal gallbladders. Histological features were systematically evaluated. Typical features in AAC were bile infiltration, leucocyte margination of blood vessels and lymphatic dilation. Bile infiltration in the gallbladder wall was more common and extended wider and deeper into the muscle layer in AAC compared with ACC. Epithelial degeneration and defects and widespread occurrence of inflammatory cells were typical features in ACC. Necrosis in the muscle layer was also more common and extended wider and deeper in ACC. There were no differences in the occurrence of capillary thromboses, lymphatic follicles or Rokitansky-Aschoff sinuses between the AAC and ACC samples. CONCLUSIONS: There are characteristic differences in histopathology between AAC and ACC, although due to overlap, none appeared to be specific as such for either condition. These results suggest that AAC is largely a manifestation of systemic critical illness, whereas ACC is a local disease of the gallbladder.

Effect of jaundice and its resolution on wound re-epithelization, skin collagen synthesis, and serum collagen propeptide levels in patients with neoplastic pancreaticobiliary obstruction.

BACKGROUND: Wound and anastomotic healing is considered to be delayed in patients with obstructive jaundice. The study was designed to find out whether the healing of experimental suction blister wounds, skin collagen synthesis, and serum procollagen levels are affected by obstructive jaundice, and if biliary drainage may cause any alterations in these processes. PATIENTS AND METHODS: Suction blisters were induced on 24 patients with obstructive jaundice caused by neoplastic pancreaticobiliary obstruction and 17 control patients with the corresponding condition without jaundice, to compare healing parameters and collagen synthesis between the groups. A second set of suction blisters were induced on 13 formerly jaundiced patients after the resolution of jaundice and on 14 control patients, to find out whether drainage or time modifies healing or collagen synthesis. By using this model, it is possible to evaluate the re-epithelization and inflammation on wound healing and to assess the baseline skin collagen synthesis. The healing of suction blisters was followed up by measuring water evaporation and blood flow in the wound. Blister fluids and serum samples were collected to study collagen propeptides. RESULTS: Healing of the blister wound was unaffected by obstructive jaundice. Drainage had no effect on healing. The baseline synthesis of type I and type III collagen in the skin was decreased in jaundiced patients. Biliary drainage improved the synthesis. Serum type III procollagen propeptide levels were elevated in jaundiced patients, but began to normalize after drainage. CONCLUSION: Healing of an experimental blister wound is not disturbed by obstructive jaundice. The decreased baseline skin collagen synthesis is partly restored by the resolution of jaundice. The results indicate that cell protein synthesis is disturbed earlier than cell dynamics in obstructive jaundice. The elevated serum PIIINP levels, which are most likely to be related to early fibrosis in liver, decreased after drainage.

The quality of life of gastroesophageal reflux disease patients waiting for an antireflux operation.

BACKGROUND: The purpose of this trial was to measure the health-related quality of life (HRQL) of gastroesophageal reflux disease (GERD) patients waiting for an antireflux operation. METHODS: A total of 120 patients waiting for a laparoscopic fundoplication were sent questionnaires measuring their symptoms and quality of life. RESULTS: Ninety-five of the patients still needing an operation returned the questionaires and were included in the analysis. Thirty-one of 84 patients (37%) felt that the symptoms had worsened, and 51/90 (57%) were unsatisfied. Thirty percent suffered from throat or airway infections, 25% from swallowing difficulties, 48% from retrosternal pain, and 18% had asthma. The mean GERD HRQL score (0-45) was 21.7 (95% confidence interval, 19.7-23.7). Short Form-36 scores of this population were significantly worse when compared to patients with inguinal hernia or moderate asthma. CONCLUSIONS: Patients waiting for a fundoplication seem to have a significantly decreased health-related quality of life due to poor symptom control regardless of continuous medical treatment.

Immunohistological distribution of the tight junction components ZO-1 and occludin in regenerating human epidermis.

BACKGROUND: Molecular characterization of tight junction proteins during the past few years has provided novel methods for studying these specialized junctions. Tight junctions have recently been characterized in the granular cell layer of human epidermis, and the role of these junctions in the epidermal barrier is now being re-evaluated. OBJECTIVES: To investigate the expression of tight junction components during the re-epithelialization of suction blisters and the regeneration of the corneal layer after tape stripping. METHODS: Suction blisters were induced in eight healthy volunteers, and skin biopsies were taken 4 or 6 days afterwards. The restoration of epidermal barrier function was evaluated by measuring water evaporation (WE) from the wound area. Tape stripping was performed on three volunteers to remove the corneal layer. The tissues were immunolabelled using indirect immunofluorescence or the avidin-biotin method. RESULTS: Prior to the biopsies, WE from the blister wounds was markedly elevated in comparison with normal skin. In the epidermis surrounding the blister, occludin and ZO-1 were expressed in the granular cell layer only. In the hyperproliferative zone adjacent to the border of the blister, the expression of ZO-1 was redistributed into several spinous cell layers, while occludin expression was restricted to the upper epidermis. In the leading edge of migrating keratinocytes, both proteins were expressed exclusively in the most superficial layer of keratinocytes. Double labelling for ZO-1 and involucrin showed expression of both proteins in the same layers of hyperproliferative keratinocytes, while the expression patterns were clearly different in the migrating keratinocytes. CONCLUSIONS: Tight junctions of regenerating epidermis may provide a functional barrier prior to regeneration of the corneal layer.

Microcirculatory response of skin to benzoic acid and methyl nicotinate in patients with diabetes.

AIMS: In view of the relationship between microvascular pathology and organ complications in diabetes mellitus, the aim of the present study was to examine the microvascular response of upper arm skin to non-immunological contact irritants in 17 insulin-dependent diabetic patients and 11 non-diabetic controls. METHODS: Non-immunological contact urticaria, an inflammatory reaction mediated in a unique way, not previously studied in diabetic patients, was examined. The test agents were benzoic acid and methyl nicotinate. The intensity of the reactions was measured using laser-Doppler flowmetry and colorimetry. The patients were divided into two groups, depending on whether they had had diabetes for less or more than 10 years. RESULTS: There were no differences in the maximal blood flow responses between the groups, but the diabetic patients showed increased blood flow responses to the lowest irritant concentrations compared to the controls. The reactions in the two groups of diabetic patients were similar. CONCLUSIONS: The present study suggests that the microvascular reactivity of diabetic skin to non-immunological contact irritants is increased.

Delayed restoration of epidermal barrier function after suction blister injury in patients with diabetes mellitus.

AIMS: Diabetes mellitus is a risk factor for compromised wound healing. The present study examines the restoration of the epidermal barrier function using the suction blister wound model. METHODS: The healing process was evaluated over time by measuring water evaporation (WE) and blood flow (BF) in the wound area. Seventeen Type 1 diabetic males and 11 non-diabetic control males were studied. RESULTS: At the onset, the WE of diabetic patients was 116 +/- 11 g x m(-2) x h(-1) and that of controls 95 +/- 13 g x m(-2) x h(-1) (P < 0.001). On the second day, the WE of diabetic patients was 90 +/- 21 g x m(-2) x h(-1) and that of controls 60 +/- 24 g x m(-2) x h(-1) (P < 0.02). The most profound difference was encountered during the fourth day, when the WE of diabetic patients was 40 +/- 17 g x m(-2) x h(-1) and that of controls 14 +/- 8 g x m(-2) x h(-1) (P < 0.001). The value recorded on the fourth day was 37% of the onset value in diabetic patients and 16% in controls (P < 0.001). Eight days after wounding the values were close to that of normal skin in both diabetic and control subjects. At the onset, the BF was 93 +/- 20 (arbitrary units) in diabetic men and 112 +/- 18 in controls (P = 0.02). On the second, fourth and eighth day there was no significant differences. CONCLUSIONS: The results suggest that restoration of the epidermal barrier function is delayed in the patients with diabetes. There were also a trend toward an initially weaker inflammatory response.

Effects of PUVA and UVB treatments on restoration of epidermal barrier function and vascular response after suction blister injury in human skin in vivo.

PUVA and UVB phototherapies are used in the treatment of psoriasis and other inflammatory skin diseases. Ultraviolet radiation causes inflammation and modulates cell kinetics in the skin. PUVA also has an inhibitory effect on skin DNA synthesis. In this study, the effects of PUVA and UVB treatments on epidermal would healing were examined using the suction blister wound model. The healing of the wound was studied indirectly by measuring water evaporation and blood flow in the wound area. On the fourth day, water evaporation was more abundant in PUVA-treated patients (42 +/- 5 g/m2h) than in UVB treated (36 +/- 4 g/m2h) or control patients (27 +/- 3 g/m2h) (analysis of variance, the least significant difference test at a level of 0.05). The P value for the difference of means between the PUVA and control groups was 0.014. Blood flow was also more abundant during the fourth (PUVA 162 +/- 11 arbitrary units, UVB 122 +/- 10, controls 115 +/- 15) and sixth (PUVA 108 +/- 18, UVB 73 +/- 17, controls 57 +/- 13) day in PUVA treated patients (analysis of variance, the least significant difference test at a level of 0.05). The results suggest that PUVA treatment decreases the restoration of the epidermal barrier function. The PUVA-treated patients also showed a more intense and prolonged vascular response that may be due to PUVA-related inflammation.

Expression of cytokeratins in regenerating human epidermis.

The expression of cytokeratin polypeptides in regenerating human epidermis was immunohistochemically examined during re-epithelization of suction blisters. The regenerating basal and suprabasal epidermis expressed keratin polypeptides K13, K14, K16 and K18, which are not present in normal suprabasal epidermis. On the contrary, K10, a normal constituent of terminally differentiated keratinocytes, was lacking from the epidermis until the ninth day of re-epithelization. The findings indicate changes similar to other hyperproliferative states (expression of K16), basal-like features (expression of K14), or properties reminiscent of fetal skin (K13 and K18) in the newly formed epidermis. Monoclonal antibodies for cytokeratins and a technique using suction blisters seemed to be a suitable methodology for the study of epidermal regeneration in normal skin. The technique may also have advantages in the investigation of keratin expression in diseased skin.

Comparison of the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo.

It has been shown previously that topical corticosteroid treatment decreases collagen synthesis in human skin in vivo and that the adverse effects are due to reduced collagen synthesis. The aim of the present study was to evaluate the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo. Fourteen healthy male volunteers applied hydrocortisone, hydrocortisone-17-butyrate, betamethasone and vehicle twice a day for one week to four separate areas marked on their abdominal skin. The collagen synthesis rate in the skin was measured by assaying collagen propeptides from the suction blisters induced on the treated areas. Aminoterminal propeptide of type I procollagen (PINP) and aminoterminal propeptide of type III procollagen (PIIINP) were measured from skin blister fluid using radioimmunoassays. Skin thickness was measured with ultrasound. Hydrocortisone decreased the two propeptides studied in the suction blister fluids less than did hydrocortisone-17-butyrate and betamethasone, but the interindividual variation was great. Hydrocortisone-17-butyrate and betamethasone had almost similar decreasing effects on the propeptides in the suction blister fluid. Hydrocortisone decreased the concentrations of PINP and PIIINP by about 35%. In some subjects (4/14) the decline of the collagen propeptide levels was over 50%. The decline in the concentration of PINP was 63% by hydrocortisone-17-butyrate and 69% by betamethasone, while the decrease in PIIINP was 55% by hydrocortisone-17-butyrate and 62% by betamethasone. None of the treatments had any effect on skin thickness within one week. In conclusion, it seems that hydrocortisone is less atrophogenic than hydrocortisone-17-butyrate and betamethasone, as shown by radioimmunoassays for collagen propeptides. The order of inhibitory potency of the three glucocorticoids on collagen synthesis was hydrocortisone < hydrocortisone-17-butyrate < betamethasone. Thus, assay of collagen propeptides from suction blisters can be used to screen various steroids with respect to their action on collagen synthesis.

Topical mometasone furoate and betamethasone-17-valerate decrease collagen synthesis to a similar extent in human skin in vivo.

Topical corticosteroids are used extensively to treat inflammatory skin diseases. Long-term use, however, may be associated with adverse effects such as skin atrophy. New steroids have been developed with the objective of increasing efficacy and reducing the incidence of adverse effects. Mometasone furoate (MMF) is one of these new derivatives. The aim of our study was to compare the effects of MMF and betamethasone-17-valerate (BM-17-valerate) on collagen synthesis in human skin in vivo. Fifteen healthy male volunteers applied MMF, BM-17-valerate and vehicle for 1 week to different areas of abdominal skin. Suction blisters were raised on these areas, and a control site, and procollagen propeptide (PICP, PINP, PIIINP) levels in the suction blister fluid were measured by radioimmunoassay. Skin thickness was measured ultrasonically by Dermascan A at the end of the treatment period. The levels of the three propeptides in suction blister fluid were reduced to similar extent by MMF and BM-17-valerate. The 1-week treatment period had no detectable influence on skin thickness. We conclude that MMF and BM-17-valerate decrease collagen synthesis to the same extent in human skin in vivo.