Lung disease severity in idiopathic pulmonary fibrosis is more strongly associated with impedance measures of bolus reflux than pH parameters of acid reflux alone.

BACKGROUND: Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF). Pathogenesis may be related to chronic micro-aspiration. We aimed to assess objective measures of GER on multichannel intraluminal impedance and pH study (MII-pH) and their relationship with pulmonary function testing (PFT) results, and to compare the performance of pH/acid reflux parameters vs corresponding MII/bolus parameters in predicting pulmonary dysfunction in IPF. METHODS: This was a retrospective cohort study of IPF patients undergoing prelung transplant evaluation with MII-pH off acid suppression, and having received PFT within 3 months. Patients with prior fundoplication were excluded. Severe pulmonary dysfunction was defined using diffusion capacity of the lung for carbon monoxide (DLCO) ≤40%. Six pH/acid reflux parameters with corresponding MII/bolus reflux measures were specified a priori. Multivariate analyses were applied using forward stepwise logistic regression. Predictive value of each parameter for severe pulmonary dysfunction was calculated by area-under-the-receiver-operating-characteristic-curve or c-statistic. KEY RESULTS: Forty-five subjects (67% M, age 59, 15 mild-moderate vs 30 severe) met criteria for inclusion. Patient demographics and clinical characteristics were similar between pulmonary dysfunction groups. Abnormal total reflux episodes and prolonged bolus clearance time were significantly associated with pulmonary dysfunction severity on univariate and multivariate analyses. No pH parameters were significant. The c-statistic of each pH parameter was lower than its MII counterpart in predicting pulmonary dysfunction. CONCLUSIONS & INFERENCES: MII/bolus reflux, but not pH/acid reflux, was associated with pulmonary dysfunction in prelung transplant patients with IPF. MII-pH may be more valuable than pH testing alone in characterizing GER in IPF.

Management of Bile Duct Injury at Various Stages of Presentation: Experience from a Tertiary Care Centre.

The clinical presentation, management and outcome of all patients with bile duct injury who presented to our tertiary care centre at various stages after cholecystectomy were analyzed. The patients were categorized into three groups: group A-patients in whom the injury was detected during cholecystectomy, group B-patients who presented within 2 weeks of cholecystectomy and group C-patients who presented after 2 weeks of cholecystectomy. Our team acted as rescue surgeons and performed 'on-table' repair for injuries occurring in another unit or in another hospital. Strasberg classification of bile duct injury was followed. In group A, partial and complete transections were managed by repair over T-tube and high hepaticojejunostomy, respectively. Patients in group B underwent endoscopic retrograde cholangiogram and/or magnetic resonance cholangiogram to evaluate the biliary tree. Those with intact common bile duct underwent endoscopic papillotomy and stenting in addition to drainage of intra-abdominal collection when present. For those with complete transection, early repair was considered if there was no sepsis. In presence of intra-abdominal sepsis an attempt was made to create controlled external biliary fistula. This was followed by hepatico jejunostomy at least after 3 months. Group C patients underwent hepaticojejunostomy at least 6 weeks after the injury. The outcome was graded into three categories: grade A-no clinical symptoms, normal LFT; grade B-no clinical symptoms, mild derangement of LFT or occasional episodes of pain or fever; grade C-pain, cholangitis and abnormal LFT; grade D-surgical revision or dilatation required. Fifty nine patients were included in the study and the distribution was group A-six patients, group B-33 patients and group C-20 patients. In group A, one patient with complete transection of the right hepatic duct (type C) and partial injury to left hepatic duct (LHD) underwent right hepaticojejunostomy and repair of the LHD over stent. Two patients with type D and three patients with type E 2 injury underwent repair over T-tube and hepaticojejunostomy, respectively. In group B, all except one of the 18 patients with type A injury underwent endoscopic papillotomy and stenting. The bile leak subsided at a mean interval of 8 days in all, except one patient who died of fulminant sepsis. Of the 15 patients with type E injury, five underwent hepaticojejunostomy after a minimum gap of 3 months. Early repair was considered in 10 patients. Twenty patients in group C underwent hepaticojejunostomy. In a mean follow-up of 40 months, the outcome was grade A in 54 patients, grade B in three patients (one from each of the three groups) and grade D in one patient (group C). The latter patient with a type E3 injury developed recurrent stricture and cholangitis necessitating percutaneous transhepatic dilatation. The high success rate of bile duct repair in the present study can be attributed to the appropriate timing, meticulous technique and the tertiary care experience.

Idiopathic pulmonary fibrosis is associated with increased impedance measures of reflux compared to non-fibrotic disease among pre-lung transplant patients.

BACKGROUND: Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF), although the mechanism remains unclear. Gastroesophageal reflux/microaspiration may lead to lung fibrosis, while increased pulmonary workload may also worsen GER. Comparing the GER profile of IPF patients to chronic obstructive pulmonary disease (COPD) patients with similar lung function may help delineate the role of GER in IPF pathogenesis. METHODS: This was a retrospective cohort study of IPF and COPD patients undergoing pre-lung transplant multichannel intraluminal impedance and pH study (MII-pH) off acid suppression at a tertiary center in 2008-2014. Patients with prior fundoplication were excluded. Baseline demographics, pulmonary function test, and MII-pH results were recorded. Univariate analyses were performed using Fisher's exact (binary variables) and Student's t (continuous variables) tests. Logistic regression was performed to adjust for potential confounders. KEY RESULTS: A total of 90 subjects (54 IPF, 36 COPD) met inclusion criteria. Compared to COPD, IPF patients had increased total reflux episodes (65.9 vs 46.1, p = 0.02), proximal reflux episodes (30.3 vs 20.3, p = 0.04), and prevalence of abnormal total reflux episodes (38.9% vs 16.7%, p = 0.02). On multivariate analyses, abnormal total reflux episodes (OR: 4.9, p = 0.05) and bolus reflux exposure time (OR: 4, p = 0.04) remained significantly associated with IPF. CONCLUSIONS & INFERENCES: Abnormal reflux was significantly more prevalent among IPF patients after controlling for lung disease severity. Gastroesophageal reflux/microaspiration likely plays a role in fibrosis in IPF. A significant portion of IPF patients had increased non-acid reflux. Therapies aiming to prevent reflux of gastric contents may be more beneficial than antisecretory medications alone in these patients.

The effect of changing sexual, marital and contraceptive behaviour on conceptions, abortions, and births.

PIP: This study proposed a model for estimating conceptions and tested the model in the Puglia region of Italy. Data were obtained from a 1989 KAP Survey among 2014 sexually active women aged 15-24 years, 25-34 years, and 35-44 years. Data for 1979 and 1994 were distributed based on the census. The model differentiated women by marital status, contraceptive use, pregnancy state, and pregnancy outcomes and wantedness. The analysis revealed differences in intensity and tempo of fertility by age. Less educated women had children at younger ages. The number of unwanted births, conceptions, and abortions was influenced by the spread of safe contraception, sex behavior of the unmarried, and the propensity to marry and have babies. Simulations revealed that increased birth control resulted in fewer abortions and influenced unwanted conceptions and births. Fertility declined in the 1980s-90s, due to later age at marriage, wanted fertility, and nonacceptors. Contraceptors increased, as did the failure rate, which led to more abortions. Simulations for 1979 and 1994 revealed changes among singles in sex and contraceptive behavior. More conceptions among singles in the 1980s were due to earlier sexual relations. Fewer conceptions in the 1990s were due to improvement in contraceptive failure. Wanted conceptions among married women declined faster than unwanted ones. Fewer unwanted conceptions were attributed to more married acceptors and safer method use. Fewer wanted conceptions were attributed to married nonacceptors and pregnancy. Couples in the 1990s who conceived due to contraceptive failure were less inclined to abort.^ieng