Pirfenidone and Nintedanib in idiopathic pulmonary fibrosis: Real-life experience in an Italian referral centre.

BACKGROUND: Idiopathic pulmonary fibrosis has a median survival time after diagnosis of 2-5 years. The main goal of treating IPF is to stabilize or reduce the rate of disease progression. Nintedanib and Pirfenidone have been a breakthrough in the management of IPF. Here we evaluated the effectiveness of Pirfenidone and Nintedanib in a population of IPF patients diagnosed in the last 12 months at Florence ILD Referral Centre. METHODS: In the last 12 months, 82 IPF patients (66 male, mean age 78.3±23.8 years) were diagnosed and started antifibrotic therapy with Pirfenidone or Nintedanib. Their clinical and functional details were analyzed retrospectively at time 0 and after 6 and 12 months of therapy. RESULTS: The median age of the patients treated with Nintedanib was higher than that of the Pirfenidone group (p<0.0001). The most common symptoms at disease onset were exertional dyspnoea and dry cough with no differences between the two groups (p<0.05). All IPF patients manifested bibasal crackles at the time of diagnosis. No significant differences in FVC, FEV1, TLC and DLCO were found at time 0 or after 6 months between patients treated with Pirfenidone and Nintedanib (p>0.05). After 1 year, lung function test parameters of patients treated with Pirfenidone had remained stable from baseline. DISCUSSION: This study emphasizes that both antifibrotic drugs appeared to be a good therapeutic choice in terms of functional stabilization, also in older patients.

Gastric emptying and orocecal transit time in pregnancy.

PURPOSE: To evaluate the effects of pregnancy on gastrointestinal function, we determined gastric emptying time, orocecal transit time, and fasting gastrointestinal hormone levels (cholecystokinin, gastrin, pancreatic polypeptide, neurotensin) in 11 women with mild dyspeptic symptoms during the first and third trimesters of their pregnancies, and again 4-6 months after delivery. METHODS: After the women ingested a disaccharide solution, orocecal transit time was determined by monitoring breath hydrogen concentrations at 10-min intervals, and values were compared with the postpartum value. Ultrasound examinations of gastric emptying were performed during the same intervals. RESULTS: The half-emptying time and the final gastric emptying time did not differ in the first and third trimesters and postpartum, but gastrointestinal transit time was significantly longer in the third trimester of pregnancy than postpartum (100.0 min [range, 50.5-240.0 min] vs 70.0 min [range, 40.5-240.0 min; P < 0.05]), respectively. Mean plasma pancreatic polypeptide values were lower in the third trimester of pregnancy than postpartum. and a negative correlation was observed between pancreatic polypeptide levels and transit time in the third trimester (r = -0.65; P = 0.0261). The plasma levels of other gastrointestinal hormones did not differ in the various periods studied. CONCLUSIONS: Our study shows that, despite evident dyspeptic symptoms, there were no significant alterations in gastric emptying or orocecal transit time during the first trimester of pregnancy. Conversely, in the third trimester, orocecal transit time was significantly longer.

Incidence and risk factors of duodenal ulcer. A retrospective cohort study.

We evaluated the incidence and risk factors of duodenal ulcer (DU) in a cohort of patients who had undergone esophagogastroduodenoscopy in our institution from 1978 to 1982, without then finding a gastric or duodenal ulcer. Six hundred and twenty-one subjects entered the study, and 526 (84.7%) were traced in 1992. Forty-one cases of DU were found, an incidence rate of 6.7 per 1,000 person-years; the male/female ratio was 2:1. The diagnoses of peptic ulcer (PU) were validated by means of medical documentation. The odds ratio of DU was 2.3 (95% confidence interval 0.8-6.3) and 3.5 (1.4-9.0) in the II and III tertile of basal acid output (BAO) compared with the I tertile, and 2.6 (0.8-8.3) and 7.0 (2.3-20.7) in the II and III tertile of maximal acid output (MAO) compared with the I tertile. Cigarette smoking and the presence of PU among siblings of DU patients were risk factors for DU. Multiple logistic regression confirmed only the association of DU with MAO, cigarette smoking, and family history. By means of a nested case-control study, the risk of developing DU was assessed in subjects with Helicobacter pylori (HP) at the biopsy of gastric mucosa performed before the ulcer diagnosis. The odds ratio of DU in HP-positive subjects was 5.0 (95% confidence interval 0.6-45). The results of this study confirm the influence of gastric acid secretion, cigarette smoking, and family history in the pathogenesis of DU and suggest that HP infection not only favors relapse but could have an important role in the onset of the disease.

Duodenogastric reflux, histology and cell proliferation of the gastric mucosa before and six months after cholecystectomy.

In order to evaluate the effects that an increase in duodenogastric reflux (DGR) has on the mucosal cell proliferation of the non-operated stomach, we made a prospective study on 13 patients (9 female and 4 male, mean age 52 years) both before and 6 months after cholecystectomy, an operation which determines a significant increase in DGR with an intact pyloric sphincter. DGR was evaluated by measuring total intragastric bile acids (dosed by an enzymatic method), and single intragastric bile acids (dosed by High Performance Liquid Chromatography) and it was expressed as Fasting Bile Reflux (FBR) in mumol/h. Gastric cell proliferation was evaluated by measuring (by High Performance Liquid Chromatography) polyamine (putrescine, spermidine and spermine) levels in biopsy specimens taken from the antrum and gastric body. The histology of the antrum and gastric body was also evaluated. After cholecystectomy, there was a significant increase in DGR (delta = 39.23 mumol/h, 95% C.L. 11.69-136.22, sign-test for matched pairs p = 0.0003). The tissue concentration of putrescine in the antrum increased significantly (delta = 8.36 mumol/g of tissue, 95% C.L. 0.34-18.01, sign-test for matched pairs p = 0.013) and there was a worsening of histological findings in the antrum (preoperative chronic atrophic gastritis rate 38.5%, postoperative 69%). In the body there were no significant variations either in polyamine levels or in histology. The increase in DGR and in putrescine concentrations in the antrum were associated negatively (Spearman's rank -0.64, 95% C.L. -0.88 to -0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective study on duodenogastric reflux and on histological changes in gastric mucosa after cholecystectomy.

The authors carried out a prospective study to evaluate variations with time in postcholecystectomy duodenogastric reflux (expressed as "fasting bile reflux" in mumol/h) and in gastric mucosal damage. Ten patients underwent (before cholecystectomy, 6 months after surgery and after a median period of 4 years from surgery) a gastric drainage to assess total (enzymatic method) and single (high performance liquid chromatography) intragastric bile acids, and a gastroscopy with biopsies of the antrum and gastric body to assess histological damage to the mucosa. The results showed that there was a progressive increase in the fasting bile reflux of total bile acids with time (precholecystectomy median value 0.295 mumol/h; 6 months control median value 12.045 mumol/h; late control medial value 19.9 mumol/h; Friedman test, P = 0.0022). Examination of the gastric mucosa at the three moments of the study showed that histological damage worsened progressively. In fact chronic atrophic gastritis of the antrum was present in 10 percent of cases before surgery and in 50 percent 4 years after, and the prevalence of chronic superficial gastritis of the body progressed from 0 to 40 percent. Studies on larger groups of patients are necessary to evaluate whether these two phenomena are correlated.

Preliminary observation on human tubal electrical activity in vivo.

The authors have set up a new technique for recording the human tubal electrical activity in vivo. A polyethylene catheter was used with six couples of electrodes placed on the tube of 5 women during simple laparohysterectomy. The slow electrical activity was recorded by means of a 8-channel paper amplifying recorder for 3-5 days from surgery. The fimbria showed frequencies between 1.25 and 3.3 c/min, the ampulla showed higher frequencies (1-5 c/min), the isthmus showed little electrical activity. The propagation signal velocity ranges between 0.25 and 0.5 cm/sec. The amplitude ranges between 50 and 200 V. The propagation occurs mainly in the distal-proximal direction.

[Inhibitory action of Hodgkin's disease patients serum on T lymphocytes E rosette forming ability (author's transl)]. / Azione inibitoria del siero di pazienti poirtatori di morbo di hodgkin sulla capacità dei linfociti di formare rosette E.

We have studied the E rosette forming-phenomenon on normal and pathologic lymphocytes after 24 hours of incubation in Fetal Calf Serum. The percentage of E rosette forming cells decreases more after incubation in Hodgkin's disease patients serum than in normal control serum. The findings suggest a specific interaction between serum factors and Hodgkin's disease lymphocytes surface receptors.