Overlapping approach Proton Pump Inhibitors/Nux vomica-Heel as new intervention for gastro-esophageal reflux management: Delphi consensus study.

BACKGROUND: Gastro-esophageal reflux disease (GERD) may affect the upper digestive tract; up to 20% of population in Western nations are affected by GERD. Antacids, histamine H2-receptor antagonists, and Proton Pump Inhibitors (PPIs) are considered the referring medications for GERD. Nevertheless, PPIs must be managed carefully because their use, especially chronic, could be linked with some adverse effects. An effective and safe alternative pharmacological tool for GERD is needed. After the identification of potentially new medications to flank PPIs, it is mandatory to revise and improve good clinical practices even through a consensus process. AIM: To optimize diagnosis and treatment guidelines for GERD through a consensus based on Delphi method. METHODS: The availability of clinical studies describing the action of the multicomponent/multitarget medication Nux vomica-Heel, subject of the consensus, is the basic prerequisite for the consensus itself. A modified Delphi process was used to reach a consensus among a panel of Italian GERD specialists on the overlapping approach PPIs/Nux vomica-Heel as a new intervention model for the management of GERD. The Voting Consensus group was composed of 49 Italian Medical Doctors with different specializations: Gastroenterology, otolaryngology, geriatrics, and general medicine. A scientific committee analyzed the literature, determined areas that required investigation (in agreement with the multiple-choice questionnaire results), and identified two topics of interest: (1) GERD disease; and (2) GERD treatment. Statements for each of these topics were then formulated and validated. The Delphi process involved two rounds of questioning submitted to the panel experts using an online platform. RESULTS: According to their routinary GERD practice and current clinical evidence, the panel members provided feedback to each questionnaire statement. The experts evaluated 15 statements and reached consensus on all 15. The statements regarding the GERD disease showed high levels of agreement, with consensus ranging from 70% to 92%. The statements regarding the GERD treatment also showed very high levels of agreement, with consensus ranging from 90% to 100%. This Delphi process was able to reach consensus among physicians in relevant aspects of GERD management, such as the adoption of a new approach to treat patients with GERD based on the overlapping between PPIs and Nux vomica-Heel. The consensus was unanimous among the physicians with different specializations, underlying the uniqueness of the agreement reached to identify in the overlapping approach between PPIs and Nux vomica-Heel a new intervention model for GERD management. The results support that an effective approach to deprescribe PPIs through a progressive decalage timetable (reducing PPIs administration to as-needed use), should be considered. CONCLUSION: Nux vomica-Heel appears to be a valid opportunity for GERD treatment to favor the deprescription of PPIs and to maintain low disease activity together with the symptomatology remission.

Systematic intraoperative cholangiography during elective laparoscopic cholecystectomy: Is it a justifiable practice?

Backgrounds/Aims: Routine execution of intraoperative cholangiography (IOC) in laparoscopic cholecystectomy (LC) is considered a good practice to help early identification of biliary duct injuries (BDIs) or common bile duct (CBD) stones. This study aimed to determine the impact of IOC during LC. Methods: This is a retrospective, monocentric study, including patients with a LC performed from January 2020 to December 2021. Results: Of 303 patients, 215 (71.0%) were in the IOC group and 88 (29.0%) in the no-IOC group. IOC was incomplete or unclear in 10.7% of patients, with a failure rate of 14.7%. Operating time was 15 minutes longer in the IOC group (p = 0.01), and postoperative complications were higher (5.1% vs. 0.0%, p = 0.03). There were three BDIs (0.99%), all included in the IOC group; only one was diagnosed intraoperatively, and the other two were identified during the postoperative course. Regarding identifying CBD stones, IOC showed a sensitivity of 77%, a specificity of 98%, an accuracy of 97.2%, a positive predictive value of 63% and a negative predictive value of 99%. Conclusions: Systematic IOC has shown no specific benefits and prolonged operative duration. IOC should be performed on selected patients or in situations of uncertainty on the anatomy.

[Acute severe respiratory distress in chronic haemodialytic patients affected by SARS-CoV-2 pneumonia: prevalence and associated factors. A single-centre experience from Cardarelli Hospital in Naples (Italy)].

Background: SARS­CoV­2-induced severe acute respiratory syndrome is associated with high mortality in the general population; however, the data on chronic haemodialysis (HD) patients are currently scarce. Methods: We performed a retrospective analysis to evaluate the onset of acute respiratory distress syndrome (ARDS) in patients with SARS­CoV­2-induced interstitial pneumonia diagnosed by PCR test and detected by high resolution computed tomography (HRCT). For each patient, we calculated a CT score between 0 and 24, based on the severity of pneumonia. The primary outcome was the onset of ARDS, detected by P/F ratio >200. We included 57/90 HD patients (age: 66.5 ±13.4 years, 61.4 % males, 42.1% diabetics, 52.6% CV disease) treated at the Cardarelli Hospital in Naples (Italy) from 1st September 2020 to 31st March 2021. All patients were treated with intermittent HD. Results: Patients who experienced ARDS had a more severe pneumonia (CT score: 15 [C.I.95%:10-21] in ARDS patients vs 7 [C.I.95%: 1-16] in no ARDS; P=0.015). Logistic regression showed that the CT score was the main factor associated with the onset of ARDS (1.12; 95% c.i.: 1.00-1.25), independently from age, gender, diabetes, chronic obstructive pulmonary disease, and prior CV disease. Thirty-day mortality was much greater in ARDS patients (83,3%) than in no-ARDS (19.3%). Conclusions: This retrospective analysis highlights that HD patients affected by SARS-CoV-2 pneumonia show an increased risk of developing ARDS, dependent on the severity of CT at presentation. This underlines once again the need for prevention strategies, in primis the vaccination campaign, for these frail patients.

Myocardial fibrosis and diastolic dysfunction in patients on chronic haemodialysis.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is linked to myocardial collagen content in many cardiac diseases. There are no data regarding such relationship in patients with end-stage renal disease (ESRD) undergoing haemodialysis. METHODS: Twenty-five patients with ESRD undergoing haemodialysis were studied by echocardiography. LV diastolic function was investigated by Doppler echocardiography, by analysing LV filling velocities at rest and during loading manoeuvres, which represent an estimate of LV filling pressure. According to the Doppler pattern, LV filling pressure in a given patient was judged to be normal or slightly increased or to be moderately or severely increased. The presence of myocardial fibrosis was estimated by ultrasound tissue characterization with integrated backscatter, which in diastole correlates with the collagen content of the myocardium. RESULTS: Integrated backscatter was higher in patients with moderate or severely increased than in patients with normal or slightly increased LV filling pressure (integrated backscatter: 51.0 +/- 9.8 vs 41.6 +/- 5.6%; P = 0.008). Integrated backscatter was a strong and independent determinant of diastolic dysfunction (odds ratio = 1.212; P = 0.040). CONCLUSION: Our data support the hypothesis that, in a selected population of patients with ESRD undergoing haemodialysis, myocardial fibrosis is associated with LV diastolic myocardial properties.

Giant basal cell carcinoma.

A 72-year-old white man presented with a large cutaneous tumor on his back. The patient said the lesion, mostly asymptomatic, had increased in size for about 7 years. Physical examination revealed a vegetating mass (Figure 1), partially ulcerated, measuring 30 x 20 cm, which easily dripped serum and blood, with small necrotic areas and a sclerotic border. Perilesional skin appeared edematous, probably owing to inflammation and impaired lymphatic flow. Clinically, there was no evidence of lymph node involvement. His family history was noncontributory. Hematologic examination revealed hypochromic microcytic anemia. Laboratory test results showed hyperuricemia and hypercholesterolemia. The patient's history revealed mild hypertension, ischemic cardiopathy treated with percutaneous transluminal coronary angioplasty and anticoagulant drugs, and moderate chronic renal insufficiency. Histologic examination of a biopsy specimen taken from the margin of the lesion displayed a superficial area of ulceration and invasion of the deeper dermis and subcutaneous tissue (Figure 2A and Figure 2B). The tumor mostly showed an adenoid pattern: gland-like structures and cystic spaces sometimes containing amorphous or granular material, surrounded by strands of basaloid cells devoid of any peripheral palisading (Figure 2C). In some areas, the adenoid pattern coexisted with infiltrated areas characterized by thin and elongated strands or cords of basaloid cells with irregular and jagged peripheral contours within a fibrous or edematous stroma (Figure 2D). Basaloid cells often revealed nuclear atypia, marked pleomorphism and hyperchromatism (Figure 2C and Figure 2D). Therefore, a diagnosis of basal cell carcinoma, adenoid subtype, was made. Magnetic resonance imaging showed a 10-cm wide thickening of the subcutaneous layer on the lumbar region, with a partial neoplastic infiltration of the muscle fascia. No evidence of metastases was found with a total body computed tomography scan. Because the patient was taking anticoagulant drugs and had unstable renal and cardiac function, surgical treatment was at least temporarily excluded, and the patient was referred for radiation therapy.

The role of interleukin-6 and of its soluble receptors in the biocompatibility of dialysis treatment.

Proinflammatory cytokines, in addition to their role in host defence, may be considered mediators of disease; a reduction of cytokine synthesis or effects is, therefore, becoming a target of many diseases. IL-6 is a pro-inflammatory cytokine that may play a role in several clinical problems related to dialysis treatment. An enhanced spontaneous production of IL-6 by Peripheral Blood Mononuclear Cells (PBMC) harvested from ESRD patients dialyzed with a poor biocompatible membrane has been first demonstrated by our group. These results were also obtained in patients undergoing continuous peritoneal dialysis, in absence of peritonitis. We have also demonstrated that IL-6 release was inversely correlated with serum albumin changes. Biological activities of IL-6 may be modulated by two soluble circulating receptors, namely sIL-6R and sgp130. sIL-6R may enhance the inflammatory effects of IL-6 and is, therefore, an "agonistically" acting molecule. We have recently studied sIL-6R production in ESRD patients dialyzed with different membranes; the conclusion was that poor biocompatible membranes, via the sIL-6R, might further increase the inflammatory effects of IL-6. On the contrary, sgp130 can efficiently bind the IL-6/sIL-6R complex with "antagonistic" effects. We have evaluated plasma levels of sgp130 in 18 ESRD patients regularly dialyzed with hemophan membranes (HE) and in 15 patients dialyzed with more biocompatible synthetic membranes (BIO). Our results demonstrate that plasma levels of sgp130 in HE are 33% higher than in both healthy controls and BIO. Circulating levels of sgp130 were correlated positively with C-reactive protein (r: 0.338, p<0.05) and negatively with serum albumin (r: -0.334, p<0.05). These results suggest that higher circulating levels of sgp130 are likely associated with higher IL-6 levels. These higher amounts are probably insufficient to control the activity of IL-6 and may be considered only as a marker of PBMC activation.