The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion.

Hypophosphatasia (HPP) is a rare genetic disorder in which pathogenic variants of the ALPL gene lead to a marked decrease of tissue non-specific alkaline phosphatase (TNSALP) activity. Although HPP is a systemic disorder, its clinical manifestations are more evident on bones, teeth, muscle and central nervous system. The clinical spectrum ranges from severe forms with extreme skeletal deformities, respiratory impairment, seizures, to very mild forms with onset in late adulthood and few clinical signs. The diagnosis can be suspected by measurement of TNSALP activity, but the insufficient awareness among health professionals and the lack of official guidelines are responsible for delayed diagnosis in children with HPP. The purpose of the current document is to provide an expert opinion directed at optimizing the diagnostic pathway of pediatric HPP. From April to December 2022, a multidisciplinary working group of 6 experts including two pediatric endocrinologists, a pediatric neurologist, a pediatric odontologist, a clinical geneticist, and a molecular biologist gathered in a series of periodic meetings to discuss the main issues related to the diagnosis of HPP in children and formalize an Expert Opinion statement. The experts agreed on a diagnostic trail that begins with the recognition of specific clinical signs, leading to biochemical analyses of TNSALP activity and vitamin B6 serum concentration. Very important are the neurological and dental manifestation of the disease that should be thoroughly investigated. The evaluation of TNSALP activity must consider sex and age variability and low activity must be persistent. Repeated blood measurements are thus necessary. The molecular analysis is then mandatory to confirm the diagnosis and for genetic counseling.

Modes and Mechanisms of Pacific Decadal-Scale Variability.

The modes of Pacific decadal-scale variability (PDV), traditionally defined as statistical patterns of variance, reflect to first order the ocean's integration (i.e., reddening) of atmospheric forcing that arises from both a shift and a change in strength of the climatological (time-mean) atmospheric circulation. While these patterns concisely describe PDV, they do not distinguish among the key dynamical processes driving the evolution of PDV anomalies, including atmospheric and ocean teleconnections and coupled feedbacks with similar spatial structures that operate on different timescales. In this review, we synthesize past analysis using an empirical dynamical model constructed from monthly ocean surface anomalies drawn from several reanalysis products, showing that the PDV modes of variance result from two fundamental low-frequency dynamical eigenmodes: the North Pacific-central Pacific (NP-CP) and Kuroshio-Oyashio Extension (KOE) modes. Both eigenmodes highlight how two-way tropical-extratropical teleconnection dynamics are the primary mechanisms energizing and synchronizing the basin-scale footprint of PDV. While the NP-CP mode captures interannual- to decadal-scale variability, the KOE mode is linked to the basin-scale expression of PDV on decadal to multidecadal timescales, including contributions from the South Pacific.

Radiation-induced undifferentiated pleomorphic sarcoma of the breast: a rare but serious complication following breast-conserving therapy. A case report and literature review.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) of the breast is an extremely rare, but aggressive subtype of sarcoma that can develop in radiotherapy (RT)-treated breast cancer patients. Due to the low incidence, there are many uncertainties regarding the adequate management of these tumors. We present a rare case of radiation-induced UPS in a 63-year-old woman who had undergone breast conserving therapy for invasive ductal carcinoma of the left breast, six years prior to presentation. CASE PRESENTATION: A 63-year-old woman presented with a rapidly growing left breast mass. She had been diagnosed with invasive ductal carcinoma of the left breast for which she underwent a left upper outer quadrantectomy and ipsilateral axillary dissection followed by RT, six years previously. During her routine oncologic follow-up, the mammography revealed a dense, nodular opacity with microcalcifications. The breast ultrasound (US) confirmed the presence of the nodule. US-guided fine needle aspiration biopsy was performed and the diagnosis of UPS was made, the reason for which the patient underwent wide local excision of the left breast. CONCLUSION: The diagnosis of RT-induced UPS is challenging and often missed due to the low incidence, long latency period, unspecific imaging findings, and difficulties in clinical and histological detection of these lesions. These tumors should be considered in differential diagnoses of rapidly-growing breast masses in previously RT-treated breast cancer patients, as they can mimic the local recurrence of the primary tumor. Since the prevalence of breast-conserving surgery followed by RT has been increasing, the careful monitoring of at risk patients is of utmost importance, as UPSs are highly aggressive tumors associated with very poor outcomes.

Laparoscopic sleeve gastrectomy for morbid obesity: role of intraluminal and intraperitoneal postoperative drainage.

BACKGROUND AND AIMS: Bleeding and staple line leak are the most common postoperative complications of LSG. To prevent and/or to promptly identify such complications, conventional peri-operative protocols imply post-operative gastric decompression (NGT) and staple line drain (IAD). Our aim was to evaluate the role of naso-gastric tube (NGT) and intra-abdominal drain (IAD) in preventing and/or facilitating identification and treatment of post-operative complications after sleeve gastrectomy. PATIENTS AND METHODS: A retrospective observational study on two consecutive series has been undertaken to evaluate the real utility of routine placement of NGT and IAD at the end of a LSG to prevent (primary end-point), promptly identify (secondary end-point) and manage (tertiary end-point) bleeding and staple line leakage. Collected outcome data of all consecutive cases, which underwent primary LSG at our Department, were analyzed. The first 100 consecutive patients (group A) received the standard perioperative protocol and the other consecutive 100 (group B) received a fast track protocol (no NGT neither IAD). RESULTS: The two groups were not different in their outcome. Two bleeding occurred in Group A and were conservatively treated. One abscess developed in group B soon after surgery. It was diagnosed by an abdominal CT performed because patients presented fever, leucocitosis and tachycardia. It was successfully treated by percutaneous ultrasound-guided drainage. One fistula occurred in group B after discharge on 30th post-operative day. Fistula was suspected based on fever and tachycardia in absence of any abdominal discomfort and was confirmed by an abdominal CT. The patient was successfully treated in 40 days by endoscopic positioning of a gastric tube-prosthesis and percutaneous ultrasound-guided drainage of abdominal collection. A third patient in group B experienced bleeding suspected due to hemoglobin drop and confirmed by abdominal CT. He also was conservatively treated. CONCLUSIONS: In conclusion, placement of drains does not facilitate detection of leak, abscess, or bleeding after primary LSG.

Supergiant fecaloma as manifestation of chronic constipation.

Fecaloma is common in patients with damage to the autonomic nervous system in the large bowel associated with Chagas disease (inflammatory and neoplastic) or Hirschprung's disease, in psychiatric patients and, more commonly, in elderly patients suffering with chronic constipation. Symptoms of fecaloma are usually nonspecific. Clinical examination can give the appearance of an abdominal tumor. Most cases of fecaloma are treated conservatively with digital evacuation and enemas. In severe and unremitting cases, surgery is required to prevent significant complications. Fecaloma should be considered in the differential diagnosis of any patient with history of chronic constipation and abdominal mass. We present the clinical case of an 85-year-old man with a history of chronic constipation presented to the emergency room with vague abdominal pain of 2 days' duration. An erect abdominal X-ray and computed tomography revealed a supergiant faecaloma extending from the pubis up to the diaphragm associated to a megarectum and megacolon. The patient was treated successfully with digital evacuation and enemas.

Does the margin width influence recurrence rate in liver surgery for hepatocellular carcinoma smaller than 5 cm?

OBJECTIVE: Liver surgery is considered a curative treatment for hepatocellular carcinoma (HCC) but the importance of resection margin width remains controversial. The aim of this study is to clarify the role of 5-10 mm surgical margin width on post-operative recurrence and overall survival after resection. PATIENTS AND METHODS: We analyzed recurrence rate and overall survival rate of 72 patients who underwent curative hepatic resection for HCC smaller than 5 cm with 5-10 mm surgical margin width between January 2005 and December 2014. RESULTS: The mean follow-up period was 36 months. Among the seventy-two patients, thirty-one (31/72; 43%) developed recurrence but only eleven (11/31; 15.3%) along the resection margin. The disease-free survival was 77.2%, 50%, 41.4% at 1, 3 and 5 years respectively, and the overall survival was 89.9%, 78.8%, 60% at 1, 3 and 5 years respectively. CONCLUSIONS: 5-10 mm surgical resection margin for HCC smaller than 5 cm seems to be safe as a wider surgical margin because does not increase the risk of marginal recurrence and does not decrease overall survival rate. Further prospective and randomized studies are required to definitively clarify the importance of surgical margin width in hepatic resection for HCC.

The role of echocardiography in the evaluation of cardiac damage in hypertensive obese patient.

Obesity rates are rising worldwide. Often obesity is associated with hypertension leading to an increased cardiovascular risk. Both obesity and hypertension induce several modifications in cardiac structure and function, particularly atrial and ventricular remodeling is a common finding shared by these two conditions. It has been demonstrated obesity leads to: left ventricular (LV) mass increase, LV systolic and diastolic dysfunction, left atrium (LA) size increase, LA function alterations and pericardial fat accumulation. Nowadays, the development of cardiac imaging techniques allows to early identifying any preclinical damage related to hypertension and obesity. This could be very important in order to improve patient management and medical therapy.

The Aquamantys® system as alternative for parenchymal division and hemostasis in liver resection for hepatocellular carcinoma: a preliminary study.

OBJECTIVE: To evaluate the clinical feasibility and safety of a new technique for liver resection using a new saline-coupled bipolar sealing device (Aquamantys®) that has shown high performance in the animal setting. PATIENTS AND METHODS: Twelve Child-Pugh A cirrhotic patients with hepatocellular carcinoma underwent partial hepatectomies using Aquamantys®. Our primary end-point was to observe occurrence of early specific surgical complications as bleeding, biliary leakage and abscess development. Our secondary end-point was to evaluate local recurrence along resection margin after a minimum follow-up of 1 year. RESULTS: One bisegmentectomy, five monosegmentectomies and six atypical resections were performed. Mean resection time was 45 minutes (range, 30-100 min). Mean blood loss was 20 mL (range 5-80 mL). Mean post-operative stay was 6 days (range 5-16 days). All specimens presented negative margins (R0) at pathological examination. No blood transfusion were required both intra-operatively and post-operatively. No mortality was observed within 30-days post-operatively. One fluid collection occurred after  6-7 bisegmentectomy and was successfully treated by ultrasound-guided percutaneous drainage. At 1 year follow-up two patients died: one because of new lesions into the liver and one because of distant metastases and multifocal new liver disease. Ten patient are alive disease free at 1 year follow-up. CONCLUSIONS: Liver resection using Aquamantys® is feasible and safe and allows to achieve almost bloodless parenchymal division with minimal necrosis and negative margins even in atipycal resection. Comparative trials are needed to confirm our preliminary results.

Pancreatic large mucinous cystoadenoma with invasive ductal carcinoma in pregnancy. Case report.

BACKGROUND: Cystic tumour of the pancreas are infrequent and malignancy of the pancreas during pregnancy is extremely rare. Mucinous cystoadenomas is the most frequent cystic pancreatic neoplasm and it is seen mainly in women suggesting a sex hormone influence. Its presentation during pregnancy is extremely rare and entails difficulties in diagnosis and therapy. CASE REPORT: A 28 year old woman was referred to our service for abdominal mass. She had given birth to her second child two weeks previously. Ultrasound and CT scan showed a large cystic lesion, with sepitation and inner solid growth portions, involved mainly the left sovramesocolic space. An ultrasound-guided aspiration of the cystic fluid showed high level of CEA and CA. 19-9. The patient underwent laparotomic body-tail pancreatectomy and splenectomy. The histological examination showed mucinous cystoadenoma with associated invasive ductal carcinoma, with ovarian-like stroma and a well delimited fibrous capsule. Hystochemical study revealed a strong positivity for progesterone receptors. CONCLUSIONS: To our knowledge this is the eighth case of mucinous cystoadenoma reported in English literature and the forth with an invasive adenocarcinoma associated. This pathological entity should always be kept in mind in case of patient with an hepigastric mass during or soon after pregnancy. Aggressive approach is mandatory.

Kneelike structure in the spectrum of the heavy component of cosmic rays observed with KASCADE-Grande.

We report the observation of a steepening in the cosmic ray energy spectrum of heavy primary particles at about 8×10(16) eV. This structure is also seen in the all-particle energy spectrum, but is less significant. Whereas the "knee" of the cosmic ray spectrum at 3-5×10(15) eV was assigned to light primary masses by the KASCADE experiment, the new structure found by the KASCADE-Grande experiment is caused by heavy primaries. The result is obtained by independent measurements of the charged particle and muon components of the secondary particles of extensive air showers in the primary energy range of 10(16) to 10(18) eV. The data are analyzed on a single-event basis taking into account also the correlation of the two observables.

Cationic distribution and spin canting in CoFe2O4 nanoparticles.

CoFe(2)O(4) nanoparticles (D(NPD) ~6 nm), prepared by a thermal decomposition technique, have been investigated through the combined use of dc magnetization measurements, neutron diffraction, and (57)Fe Mössbauer spectrometry under high applied magnetic field. Despite the small particle size, the value of saturation magnetization at 300 K (M(s) Í = 70 A m(2) kg(-1)) and at 5 K (M(s) Í = 100 A m(2) kg(-1)) are rather close to the bulk values, making the samples prepared with this method attractive for biomedical applications. Neutron diffraction measurements indicate the typical ferrimagnetic structure of the ferrites, showing an inversion degree (γ(NPD) = 0.74) that is in very good agreement with cationic distribution established from low temperature (10 K) Mössbauer measurements in high magnetic field (γ(moss) = 0.76). In addition, the in-field Mössbauer spectrum shows the presence of a non-collinear spin structure in both A and B sublattices. The results allow us to explain the high value of saturation magnetization and provide a better insight into the complex interplay between cationic distribution and magnetic disorder in ferrimagnetic nanoparticles.

Heterogeneous expression of cyclooxygenase-2 and inducible nitric oxide synthase within colorectal tumors: correlation with tumor angiogenesis.

BACKGROUND: Recent studies have shown that the cyclooxygenase (COX) and the inducible nitric oxide synthase (iNOS) pathways are involved in the development of tumor angiogenesis in human cancers. AIMS: To investigate whether a different pattern of COX-2 and iNOS expression/activity exists within different areas of colorectal tumors and to analyze the relationship between these two enzymes and tumor angiogenesis. METHODS: Microvessel density (MVD) and COX-2, iNOS, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein expression were evaluated at both the invasive front (IF) and the tumor center (TC) in 46 human colorectal cancer specimens. We also investigated the concentration of PGE2 and NO at the same sites. RESULTS: COX-2 and iNOS protein expression and activity were significantly higher within the IF than the TC of the tumor specimens. Similarly, MVD and VEGF/VEGFR-2 expression significantly increased from the TC to the IF. Only COX-2 expression was significantly correlated with MVD and VEGF/VEGFR-2 expression at both the TC and the IF. CONCLUSION: Our study shows a heterogeneous expression of COX-2 and iNOS in colorectal cancer. The up-regulation of COX-2 at the IF parallels an increase in vessel density and VEGF/VEGFR-2 expression, thus supporting the hypothesis that the tumor periphery is the most aggressive portion of a colorectal tumor.

Radiofrequency-assisted liver resection in patients with hepatocellular carcinoma and cirrhosis: preliminary results.

Radiofrequency (RF)-assisted liver resection has been shown to allow virtually bloodless procedures without the need for vascular exclusion maneuvers. The aim of this study was to evaluate the safety and feasibility of RF-assisted liver resection in cirrhotic patients with hepatocellular carcinoma (HCC) and, moreover, to assess whether the RF-assisted procedure influenced the outcomes in terms of morbidity and mortality. This retrospective study included 39 cirrhotic patients who underwent RF-assisted liver resection for HCC between September 2001 and March 2006. In this period, we performed 17 monosegmentectomies, 16 bisegmentectomies, 4 trisegmentectomies, and 2 right hepatectomies. We never performed vascular exclusion maneuvers. Blood transfusion was necessary in 3 cases. One patient died postoperatively because of untreatable hepatorenal syndrome. The morbidity rate was 23%. Among patients without postoperative morbidity (n = 30), the 4-year survival rate was 61% versus 23% in patients who experienced postoperative morbidity (n = 9; P < .05). The 4-year disease-free survival rate was 40% in patients without postoperative morbidity versus 10% in patients who experienced postoperative morbidity (P = .05). Tumor dimension, number of lesions, and Child-Pugh class at surgery did not seem to significantly influence the 4-year overall survival (P > .05). In conclusion, RF-assisted liver resection was a safe, feasible procedure associated with low morbidity and hospital mortality rates even in cases of liver cirrhosis. It is, in our opinion, highly recommended for patients with HCC not suitable for liver transplantation.

Laparoscopic Habib 4X: a bipolar radiofrequency device for bloodless laparoscopic liver resection.

BACKGROUND: In recent years the progress of laparoscopic procedures and the development of new and dedicated technologies have made laparoscopic hepatic surgery feasible and safe. In spite of this laparoscopic liver resection remains a surgical procedure of great challenge because of the risk of massive bleeding during liver transection and the complicated biliary and vascular anatomy in the liver. A new laparoscopic device is reported here to assist liver resection laparoscopically. METHODS: The laparoscopic Habib 4X is a bipolar radiofrequency device consisting of a 2 x 2 array of needles arranged in a rectangle. It is introduced perpendicularly into the liver, along the intended transection line. It produces coagulative necrosis of the liver parenchyma sealing biliary radicals and blood vessels and enables bloodless transection of the liver parenchyma. RESULTS: Twenty-four Laparoscopic liver resections were performed with LH4X out of a total of 28 attempted resections over 12 months. Pringle manoeuvre was not used in any of the patients. None of the patients required intraoperative transfusion of red cells or blood products. CONCLUSION: Laparoscopic liver resection can be safely performed with laparoscopic Habib 4X with a significantly low risk of intraoperative bleeding or postoperative complications.

Ultrasound-guided radiofrequency-assisted segmental arterioportal vascular occlusion in laparoscopic segmental liver resection.

BACKGROUND: Studies have shown laparoscopic liver resection to be feasible and safe. Segmental hepatectomy is appealing because it allows a reduction of intraoperative blood loss and blood replacement by dividing tissues along the anatomic planes. However, an effective technique that allows the closure of segmental vessels during systematic segmentectomies before resection still is lacking in laparoscopic surgery. METHODS: A simple technique guided by intraoperative ultrasound to facilitate laparoscopic liver segmentectomies is described. Coagulative desiccation of the vessels feeding the segment to be resected was induced by introduction of a "cooled-tip" radiofrequency electrode percutaneously under intraoperative ultrasound guidance at the level of the vessels. The intrahepatic parenchymal change induced by the radiofrequency was monitored using intraoperative ultrasound. After the application of energy to destroy the vessels feeding that segment, an area of marked discoloration on the surface of the liver became obvious. Liver parenchymal transection followed without any form of hepatic inflow occlusion. RESULTS: For this study, 10 patients underwent a segmental resection using the described technique. The resection time ranged from 40 to 60 min including the time required to destroy the feeding vessels with radiofrequency. The intraoperative blood loss was less than 50 ml and did not necessitate intra- or postoperative blood transfusion. The surgical margins of the specimen were free of disease. There was no morbidity or mortality. CONCLUSIONS: The preliminary experience shows that the reported technique is safe and effective, with the potential to make even difficult laparoscopic liver segmentectomies for segments such as VII and VIII, easier to manage.

Structural characterization study of FeCo alloy nanoparticles in a highly porous aerogel silica matrix.

A series of FeCo-SiO(2) nanocomposite aerogels having different FeCo loadings of 3, 5, and 8 wt % were prepared using a novel urea-assisted sol-gel route. The size of the nanoparticles, which was estimated using Scherrer analysis of the main peak of the x-ray diffraction pattern, varies from 3 to 8 nm. X-ray absorption fine structure (EXAFS) and x-ray absorption near edge structure (XANES) techniques at both Fe and Co K edges were used to investigate the structure of the FeCo nanoparticles. EXAFS and XANES show that FeCo nanoparticles have the typical bcc structure. Evidence of oxidation was observed in low FeCo content aerogels. Spatially resolved electron energy loss spectroscopy analysis suggests the formation of a passivation layer of predominantly iron oxide.

Palliative antecolic isoperistaltic gastrojejunostomy: a randomized controlled trial comparing open and laparoscopic approaches.

Gastric outlet obstruction is a common, often preterminal, event for patients with inoperable neoplasms of the distal stomach, duodenum, and biliopancreatic area. It can be surgically managed by open or laparoscopic gastrojejunostomy. This study aimed to compare the results of open and laparoscopic palliative gastrojejunostomy for patients with gastric outlet obstruction resulting from inoperable neoplasms. A total of 24 patients were randomized prospectively to undergo laparoscopic (12 patients) or open (12 patients) palliative laterolateral antecolic isoperistaltic gastrojejunostomy. All the procedures were completed as planned. The mean duration of surgery was not significantly different between the two groups (p = 0.75). The mean intraoperative blood loss was significantly less after laparoscopic gastrojejunostomy (LGJ) (p = 0.0001). Time to oral solid food intake was longer after open gastrojejunostomy (OGJ) (p = 0.04). Two patients in the OGJ group experienced postoperative delayed gastric empting, whereas no patients in the LGJ group experienced such a complication (p = 0.04). The mean postoperative stay was shorter in the LGJ group, but the difference did not reach statistical significance (p = 0.65). No readmissions were registered after a minimum follow-up period of 2 months. The findings show that LGJ is a safe, feasible, and effective alternative to OGJ. However, because the current data involved only a small number of patients, large studies still are required for further evaluation of the this operation's effectiveness.

[Do we agree on the technical quality of our chest X-rays? A radiologist, an expert in X-ray diagnosis, and a family doctor try to find out]. / 'Estamos de acuerdo con la calidad técnica de nuestras radiografías de tórax? Un radiólogo, un técnico especialista en radiodiagnóstico y un médico de familia intentan corroborarlo.

OBJECTIVE: To appraise the degree of concordance in the interpretation of the technical quality of chest x-rays at a health centre between an expert in x-ray diagnosis, a family doctor, and a radiologist. DESIGN: Transversal study. Setting. Primary care. Cartuja Health Centre, Granada, Spain. PARTICIPANTS: Patients at the Cartuja Health Centre who had a simple chest x-ray in 2002. 150 studies were chosen by simple randomised sampling. Two were rejected because they dealt with a repeat examination of the same patient and seven because they did not reach minimum quality. The final sample was 141 x-rays. MAIN MEASUREMENTS: The observers filled in independently, for each examination, an 11-item protocol on the technical quality of the images. The kappa index between pairs of observers was calculated for each item, as was the overall kappa index. RESULTS: 96% of the examinations were conducted with large x-ray plates (3543). There was only acceptable or good concordance between the 3 observers in 2 questions (kappa, 0.559-0.858). In 5 questions concordance was homogeneously low (kappa, 0.034-0.375). In some questions there was a strong discrepancy between the appraisal of the expert and that of the 2 other observers. CONCLUSIONS: General concordance can be considered low, although it is somewhat greater between the radiologist and the family doctor than between either of these and the expert. This poses the need to improve professional training in evaluation of the technical quality of images. In addition, there was unnecessary expense in large-size x-ray plates.