Early prolonged prone position in noninvasively ventilated patients with SARS-CoV-2-related moderate-to-severe hypoxemic respiratory failure: clinical outcomes and mechanisms for treatment response in the PRO-NIV study.

BACKGROUND: Whether prone position (PP) improves clinical outcomes in COVID-19 pneumonia treated with noninvasive ventilation (NIV) is unknown. We evaluated the effect of early PP on 28-day NIV failure, intubation and death in noninvasively ventilated patients with moderate-to-severe acute hypoxemic respiratory failure due to COVID-19 pneumonia and explored physiological mechanisms underlying treatment response. METHODS: In this controlled non-randomized trial, 81 consecutive prospectively enrolled patients with COVID-19 pneumonia and moderate-to-severe (paO2/FiO2 ratio < 200) acute hypoxemic respiratory failure treated with early PP + NIV during Dec 2020-May 2021were compared with 162 consecutive patients with COVID-19 pneumonia matched for age, mortality risk, severity of illness and paO2/FiO2 ratio at admission, treated with conventional (supine) NIV during Apr 2020-Dec 2020 at HUMANITAS Gradenigo Subintensive Care Unit, after propensity score adjustment for multiple baseline and treatment-related variables to limit confounding. Lung ultrasonography (LUS) was performed at baseline and at day 5. Ventilatory parameters, physiological dead space indices (DSIs) and circulating inflammatory and procoagulative biomarkers were monitored during the initial 7 days. RESULTS: In the intention-to-treat analysis. NIV failure occurred in 14 (17%) of PP patients versus 70 (43%) of controls [HR = 0.32, 95% CI 0.21-0.50; p < 0.0001]; intubation in 8 (11%) of PP patients versus 44 (30%) of controls [HR = 0.31, 95% CI 0.18-0.55; p = 0.0012], death in 10 (12%) of PP patients versus 59 (36%) of controls [HR = 0.27, 95% CI 0.17-0.44; p < 0.0001]. The effect remained significant within different categories of severity of hypoxemia (paO2/FiO2 < 100 or paO2/FiO2 100-199 at admission). Adverse events were rare and evenly distributed. Compared with controls, PP therapy was associated with improved oxygenation and DSIs, reduced global LUS severity indices largely through enhanced reaeration of dorso-lateral lung regions, and an earlier decline in inflammatory markers and D-dimer. In multivariate analysis, day 1 CO2 response outperformed O2 response as a predictor of LUS changes, NIV failure, intubation and death. CONCLUSION: Early prolonged PP is safe and is associated with lower NIV failure, intubation and death rates in noninvasively ventilated patients with COVID-19-related moderate-to-severe hypoxemic respiratory failure. Early dead space reduction and reaeration of dorso-lateral lung regions predicted clinical outcomes in our study population. CLINICAL TRIAL REGISTRATION: ISRCTN23016116 . Retrospectively registered on May 1, 2021.

Epidemiology, clinical-treatment patterns and outcome in 256 hepatocellular carcinoma cases.

AIM: To analyze the epidemiology, clinical characteristics, treatment patterns and outcome in hepatocellular carcinoma (HCC) patients. METHODS: We analyzed clinical, pathological and therapeutic data from 256 consecutive patients, examined at S. Croce Hospital in Cuneo-Piedmont, with a diagnosis of HCC between 30(th) June 2000 and 1(st) July 2010. We analyzed the hospital imaging database and examined all medical records, including the diagnosis code for HCC (155.0 according to the ICD-9M classification system), both for inpatients and outpatients, and discovered 576 relevant clinical records. After the exclusion of reports relating to multiple admissions for the same patient, we identified 282 HCC patients. Moreover, from this HCC series, we excluded 26 patients: 1 patient because of an alternative final diagnosis, 8 patients because of a lack of complete clinical data in the medical record and 17 patients because they were admitted to different health care facilities, leaving 256 HCC patients. To highlight possible changes in HCC patterns over the ten-year period, we split the population into two five-year groups, according to the diagnosis period: 30(th) June 2000-30(th) June 2005 and 1(st) July 2005-1(st) July 2010. Patients underwent a 6-mo follow up. RESULTS: Two hundred and fifty-six HCC patients were included (male/female 182/74; mean age 70 years), 133 in the first period and 123 in the second. Hepatitis C virus (HCV) infection was the most common HCC risk factor (54.1% in the first period, 50.4% in the second; P = 0.63); in the first period, 21.8% of patients were alcoholics and 15.5% were alcoholics in the second period (P > 0.05); the non-viral/non-alcoholic etiology rate was 3.7% in the first period and 20.3% in the second period (P < 0.001). Child class A patients increased significantly in the second period (P < 0.001). Adjusting for age, gender and etiology, there was a significant increase in HCC surveillance during the second period (P = 0.01). Differences between the two periods were seen in tumor parameters: there was an increase in the number of unifocal HCC patients, from 53 to 69 (P = 0.01), as well as an increase in the number of cases where the HCC was < 3 cm [from 22 to 37 (P = 0.01)]. The combined incidence of stage Barcelona Clinic Liver Cancer 0 (very-early) and A (early) HCC was 46 (34.6%) between 2000-2005, increasing to 62 (50.4%) between 2005-2010 (P = 0.01). Of the patients, 62.4% underwent specific treatment in the first group, which increased to 90.2% in the second group (P < 0.001). Diagnosis period (P < 0.01), Barcelona-Clinic Liver Cancer stage (P < 0.01) and treatment per se (P < 0.05) were predictors of better prognosis; surveillance was not related to survival (P = 0.20). CONCLUSION: This study showed that, between 2000-2005 and 2005-2010, the number of HCV-related HCC decreased, non-viral/non alcoholic etiologies increased and of surveillance programs were more frequently applied.

A shift from distal to proximal neoplasia in the colon: a decade of polyps and CRC in Italy.

BACKGROUND: In the last years a trend towards proximalization of colorectal carcinomas (CRC) has been reported. This study aims to evaluate the distribution of CRC and adenomatous polyps (ADP) to establish the presence of proximalization and to assess the potential predictors. METHODS: We retrieved histology reports of colonic specimens excised during colonoscopy, considering the exams performed between 1997 and 2006 at Cuneo Hospital, Italy. We compared the proportion of proximal lesions in the period 1997-2001 and in the period 2002-2006. RESULTS: Neoplastic lesions were detected in 3087 people. Proximal CRC moved from 25.9% (1997-2001) to 30.0% (2002-2006). Adjusting for sex and age, the difference was not significant (OR 1.23; 95% CI: 0,95-1,58). The proximal ADP proportion increased from 19.2% (1997-2001) to 26.0% (2002-2006) (OR: 1.43; 95% CI: 1.17-1.89). The corresponding figures for advanced proximal ADP were 6.6% and 9.5% (OR: 1.48; 95% CI: 1.02-2.17). Adjusting for gender, age, diagnostic period, symptoms and number of polyps the prevalence of proximal advanced ADP was increased among people ≥ 70 years compared to those aged 55-69 years (OR 1.49; 95% CI: 1.032.16). The main predictor of proximal advanced neoplasia was the number of polyps detected per exam (> 1 polyp versus 1 polyp: considering all ADP: OR 2.16; 95% CI: 1.59-2.93; considering advanced ADP OR 1.63; 95% CI: 1.08-2.46). Adjusting for these factors, the difference between the two periods was no longer significant. CONCLUSIONS: CRC do not proximalize while a trend towards a proximal shift in adenomas was observed among people ≥ 70 years.

A new method of jejunal reconstruction after pancreaticoduodenectomy.

Although advances in pancreatic surgery have reduced mortality rates, post-operative morbidity remains a frequent problem in patients undergoing pancreaticoduodenectomy. The single most significant cause of morbidity in these patients is the development of pancreatic fistula. In this study, we assessed the occurrence of pancreatic fistula after isolated Roux loop pancreaticojejunostomy with the use of a haemostatic collagen-fibrin patch (TachoSil) to prevent pancreatic leakage. A total of 27 patients (15 men and 12 women, mean age 59 years, range 19-74 years) underwent proximal Whipple-type resection. Ten patients underwent a classical pancreaticoduodenectomy while a pylorus-preserving pancreaticoduodenectomy was performed in the other 17 patients. Reconstruction was done using three-jejunal anastomosis, with TachoSil applied at the end of the pancreatic jejunal anastomosis, along the entire anastomotic circumference. None of the 27 patients who underwent pancreaticoduodenectomy developed pancreatic fistula. One patient had bleeding from the gastro-jejunal anastomoses, five patients had infections of surgical sites, and three patients developed bacterial pneumonia. There were no significant differences in duration of surgery or intra-operative blood loss between patients with soft or hard pancreatic tissue. The reconstruction technique described here with three independent jejunal loops appears to offer good protection against pancreatic leakage.

Primary hepatic carcinoid: a case report and literature review.

Carcinoids are tumors derived from neuroendocrine cells and often produce functional peptide hormones. Approximately 54.5% arise in the gastrointestinal tract and frequently metastasize to the liver. Primary hepatic carcinoid tumors (PHCT) are extremely rare; only 95 cases have been reported. A 65-year-old man came to our attention due to occasional ultrasound findings in absence of clinical manifestations. His previous medical history, since 2003, included an echotomography of the dishomogeneous parenchymal area but no focal lesions. A computed tomography scan performed in 2005 showed an enhanced pseudonodular-like lesion of about 2 cm. Cholangio-magnetic resonance imaging identified the lesion as a possible cholangiocarcinoma. No positive findings were obtained with positron emission tomography. Histology suggested a secondary localization in the liver caused by a low-grade malignant neuroendocrine tumor. Immunohistochemistry was positive for anti chromogranin antibodies, Ki67 antibodies and synaptophysin. Octreoscan scintigraphy indicated intense activity in the lesion. Endoscopic investigations were performed to exclude the presence of extrahepatic neoplasms. Diagnosis of PHCT was established. The patient underwent left hepatectomy, followed by hormone therapy with sandostatine LAR. Two months after surgery he had a lymph nodal relapse along the celiac trunk and caudate lobe, which was histologically confirmed. The postoperative clinical course was uneventful, with a negative follow-up for hematochemical, clinical and radiological investigations at 18 mo post-surgery. Diagnosis of PHCT is based principally on the histopathological confirmation of a carcinoid tumor and the exclusion of a non-hepatic primary tumor. Surgical resection is the recommended primary treatment for PHCT. Recurrence rate and survival rate in patients treated with resection were 18% and 74%, respectively.

Effects of dimethyl sulfoxide, pyrrolidine dithiocarbamate, and methylprednisolone on nuclear factor-kappaB and heat shock protein 70 in a rat model of hemorrhagic shock.

BACKGROUND: Nuclear factor kappa B (NF-kappaB) is a transcription factor involved in the inflammatory response. Heat shock protein 70 (HSP70) is involved in the cell protection from various stresses. The aim of this study was to evaluate the effects of dimethyl sulfoxide (DMSO), pyrrolidine dithiocarbamate (PDTC), and methylprednisolone (MP) on liver, renal, and intestinal activation of NF-kappaB and HSP70 in a rat model of hemorrhagic shock (HS). METHODS: Sixty rats were randomized in 6 groups: sham-operated; only HS; HS and resuscitation with blood plus normal saline (NS); HS and resuscitation with blood/NS and 6 mg/kg DMSO; HS and resuscitation with blood/NS and 100 mg/kg PDTC; HS and resuscitation with blood/NS and 30 mg/kg MP. Rats were subjected to HS by blood removal to a mean arterial pressure of 35 to 40 mm Hg through the femoral artery. After 1-hour shock-period, the animals were resuscitated according to the experimental protocol. NF-kappaB and HSP70 expression in liver, kidney, and small intestine was analyzed 1 and 3 hours after resuscitation by immunohistochemistry. RESULTS: HS upregulated NF-kappaB activation and HSP70 expression (p < 0.05). Resuscitation was not associated with a further increase in NF-kappaB and HSP70 activation. DMSO, PDTC, and MP administration resulted in a decreased liver, renal, and intestinal activation of NF-kappaB associated with an increase of HSP70 expression (p < 0.05). CONCLUSIONS: Our results suggest that treatment with DMSO, PDTC, and MP can modulate the expression of NF-kappaB and HSP70 after HS in rats. This modulation may have potential effects in HS through inhibition of the NF-kappaB-dependent production of proinflammatory mediators.

Acute nonspecific abdominal pain: A randomized, controlled trial comparing early laparoscopy versus clinical observation.

AIMS: To evaluate, in a prospective, randomized, single-institution trial, the role of early laparoscopy in the management of nonspecific abdominal pain (NSAP) in young women. PATIENTS AND METHODS: Women aging from 13 to 45 years, admitted for NSAP at the emergency department, were included in the study. Exclusion criteria were pregnancy, previous appendectomy, contraindications to laparoscopy, diagnosis of malignancy, or chronic disease. NSAP was defined as an abdominal pain in right iliac or hypogastric area lasting more than 6 hours and less than 8 days, without fever, leukocytosis, or obvious peritoneal signs and uncertain diagnosis after physical examination and baseline investigations including abdominal sonography. Patients were randomly assigned to early (<12 hours from admission) laparoscopy group (LAP) or to clinical observation group (OBS). After discharge a follow-up was carried out. RESULTS: From January 2001 to February 2004, 508 female patients without previous abdominal surgery were evaluated in admitting area for acute right iliac or hypogastric abdominal pain, in 373 patients diagnosis was established for obvious signs or with baseline investigations. Of the remaining 135 patients, 31 were excluded from study for various reasons, 53 patients were randomly assigned to LAP and 51 to OBS. Groups were similar for age, mean BMI, white blood cell count, and duration of pain. During hospitalization diagnosis was established in 83.4% of the LAP and in 45.1% of OBS (P < 0.05). Twenty patients of OBS (39.2%) were operated during observation because of worsening of symptoms or appearance of peritoneal sign. Diagnoses in LAP were appendicitis in 16 patients (30.1%), pelvic inflammatory disease in 7 (13.2%), carcinoid in 1 (1.9%), other in 18 (33.9%), no diagnosis in 11 (20.7%); diagnoses in OBS were appendicitis in 3 patients (5.8%), pelvic inflammatory disease in 8 (15.6%), other in 12 (23.5%), and no diagnosis in 28 (54.9%). Mean length of hospital stay was 3.7 +/- 0.8 days in LAP and 4.7 +/- 2.4 days in OBS (P < 0.05); no differences were found regarding mortality, morbidity, radiation dose, and analgesia. Mean follow-up time was 29.3 months (range, 12-60 months) for LAP and 30.6 months for OBS (range, 12-60 months). After 3 months from discharge, 20% of patients in LAP and 52% in OBS had recurrent abdominal pain (P < 0.05); after 12 months, 16% in LAP and 25% in OBS (P = not significant). Six patients in OBS required readmission for surgery. CONCLUSIONS: Compared with active clinical observation, early laparoscopy did not show a clear benefit in women with NSAP. A higher number of diagnosis and a shorter hospital stay in the LAP group did not led to a significant reduction in symptoms recurrences at 1 year.