Elevated sweat chloride test: is it always cystic fibrosis?

BACKGROUND: The sweat chloride test (ST) is the gold standard for cystic fibrosis (CF) diagnosis in symptomatic patients, within the newborn screening and in the follow-up of CF patients during molecular therapies. However, false positives have been reported in patients with different diseases. We describe and discuss 4 cases due to different clinical conditions in which we recorded false positive ST, and the test remained altered for a period of varying length. CASES PRESENTATION: Case 1: Eight months old female child suffering from constipation, recurrent vomiting and failure to thrive, family history of recurrent pancreatitis without mutations in the PRSS1 and SPINK1 genes. Both ST and fecal elastase were altered although no CFTR gene mutations were found. Due to rapid clinical deterioration, celiac disease was suspected and diagnosed by laboratory tests and intestinal biopsy. After 2 weeks of gluten-free diet ST and fecal elastase normalized. Case 2: 14 months old male suffering from bilateral renal dysplasia, episodes of metabolic alkalosis, recurrent respiratory infections and recurrent vomiting. The child had more ST positives, but no CFTR mutations were found. During follow-up, he developed sensorineural hearing loss and an atrial septic defect was found. Finally, a diagnosis of Klinefelter was made, but the ST normalized several years later. Case 3 and 4: Two boys with stubborn constipation and fecal occlusion treated with Poly Ethylene Glycol (PEG) with salts showed pathological ST. The test returned normal a few days after stopping treatment. CONCLUSIONS: We hypotesized the possible causes of ST alteration in these conditions: in celiac disease it could be due to a transient dysregulation of the aquaporins, rapidly reversed by the diet; in Klinefelter, it may be due to stable pubertal hypoandrogenism; while, the PEG formulation itself contains salts that can temporarily alter ST.

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

This corrects the article DOI: 10.1038/cdd.2016.22.

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts 'on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment.

Deep neck infection: a present-day complication. A retrospective review of 83 cases (1998-2001).

Deep neck infections are less and less frequent today than in the past. Nevertheless, their complications are often life-threatening. The present study reviews the experience of the Department of Otolaryngology and Head and Neck Surgery of Padua with deep neck infections during the period from 1998 to 2001. Eighty-three patients (55 males and 28 females) were retrospectively considered. The site of origin of deep neck infection was identified in 76 patients (91%). The most common cause was dental infection, occurring in 35 cases (42%). In 12 cases (14%) deep neck infection was a complication of oropharyngeal infection. The relatively high incidence of Peptostreptococcus sp, Streptococcus viridans, Streptococcus intermedius and constellatus isolation was consistent with the high rate of odontogenic cases. Surgery was advocated as the treatment for any infection of the deep neck spaces. The recent series has demonstrated that medical treatment did not seem to increase complication rates or mortality. Our tailored approach (medical or medical and surgical) based on clinical and radiological evidence was successful in 97% of the patients.

The role of surgical treatment in colon diverticulitis: indications and results.

PURPOSE: Colon diverticulitis is a common illness with affects 37-45% of western populations. Indications regarding therapy guidelines, operative timing and which surgical procedure to perform are still controversial. MATERIAL AND METHOD: Between January 1977 and December 1997, 239 patients, diagnosed with diverticulitis, have been admitted, on emergency, to our Department of General Surgery; 135 males (56%) and 104 females (44%), (mean age of 63 years). RESULTS AND DISCUSSION: Forty-two patients (18%), clearly diagnosed with diffuse or local peritonitis, underwent delayed emergency surgical procedure; 44 (22%) out of 197 patients, treated with medical therapy and subsequently underwent elective surgery procedures for complications (fistulas or stenosis). Among the 42 patients treated in emergency, 26 cases (62%) underwent to resection with immediate reconstruction. Among the elective surgery group 39 (89%) out of 44 underwent to resection with immediate reconstruction. Complications reached 40% in the group of emergency patients (mortality rate 12%) and 16% in the elective surgery group (mortality rate 2%). Several features possible influencing mortality rate have been analysed; age > 70 years, acute associated diseases, generalised peritonitis and surgical timing show a statistical significance. CONCLUSION: Therefore, a careful evaluation of the patients, an appropriate pre and post-operative medical treatment, with a wider use of the most recent techniques such as CT scan guided drain, intra-operative wash-out and peritoneal lavage are recommended in order to reduce morbidity and mortality.