Variability in Diagnosis and Management of Hypoglycemia in Neonatal Intensive Care Unit.

OBJECTIVE: Hypoglycemia, the most common metabolic derangement in the newborn period remains a contentious issue, not only due to various numerical definitions, but also due to limited therapeutical options which either lack evidence to support their efficacy or are increasingly recognized to lead to adverse reactions in this population. This study aimed to investigate neonatologists' current attitudes in diagnosing and managing transient and persistent hypoglycemia in newborns admitted to the Neonatal Intensive Care Unit (NICU). METHODS: A web-based electronic survey which included 34 questions and a clinical vignette was sent to U.S. neonatologists. RESULTS: There were 246 survey responses with most respondents using local protocols to manage this condition. The median glucose value used as the numerical definition of hypoglycemia in first 48 hours of life (HOL) for symptomatic and asymptomatic term infants and preterm infants was 45 mg/dL (2.5 mmol/L; 25-60 mg/dL; 1.4-3.3 mmol/L), while after 48 HOL the median value was 50 mg/dL (2.8 mmol/L; 30-70 mg/dL; 1.7-3.9 mmol/L). There were various approaches used to manage transient and persistent hypoglycemia that included dextrose gel, increasing caloric content of the feeds using milk fortifiers, using continuous feedings, formula or complex carbohydrates, and use of various medications such as diazoxide, glucocorticoids, and glucagon. CONCLUSION: There is still large variability in current practices related to hypoglycemia. Further research is needed not only to provide evidence to support the values used as a numerical definition for hypoglycemia, but also on the efficacy of current strategies used to manage this condition. KEY POINTS: · Numerical definition of glucose remains variable.. · Strategies managing transient and persistent hypoglycemia are diverse.. · There is a need for further research to investigate efficacy of various treatment options..

A rare description of pure partial trisomy of 16q12.2q24.3 and review of the literature.

Trisomy 16 is the most common autosomal trisomy in humans, which is almost uniformly embryonic lethal. Partial trisomy 16 including a segment of the long arm of chromosome 16 is occasionally compatible with life and has been associated with severe congenital defects, growth retardation, and early lethality. Segmental trisomy of 16q is usually described concomitantly with partial monosomy of another chromosome, often resulting from a parental balanced translocation. Pure partial chromosome 16q trisomy is exceedingly rare. About nine children with 16q12→qter and 16q13→qter duplication have been reported in the literature, almost all described with monosomy of a second chromosome, and highlighting very few long-term survivors. A single individual with pure partial distal 16q12.1q23.3 duplication has been reported in an infant, underscoring complexities of genetic counseling and management, especially in view of life-limiting congenital anomalies in rare survivors. Here, we present a 12-month-old child with pure 16q12.2q24.3 trisomy, having continued morbidity related to pulmonary hypertension and chronic lung disease. The features of intrauterine growth retardation, facial dysmorphism, hypotonia, congenital heart defect, distal contractures, urogenital abnormalities, and hearing loss support the association with 16q partial trisomy, as in previous studies. This report expands our current understanding related to the survival of infants with large segmental aneusomy of the long arm of chromosome 16.

Rhizopus Infection in a Preterm Infant: A Novel Use of Posaconazole.

Posaconazole is a triazole antifungal with activity against Rhizopus, but data on its use and pharmacokinetics in preterm infants are scarce. In this case, a 24 4/7-week neonate's Rhizopus infection is successfully treated with debridement and combination antifungal therapy with amphotericin B, micafungin and enteral posaconazole. This is the first reported posaconazole use in a preterm neonate with Rhizopus.

Gastric Metastasis of Invasive Lobular Breast Carcinoma, a Current Diagnostic and Treatment Challenge - A Review.

Introduction: The predilection of lobular invasive breast cancer metastasis for the stomach is a topic that has succumbed to various assumptions over the time. Background and Aims: Gastric metastasis of lobular breast cancer is unusual and it can be diagnosed after a long period of time from primary tumor diagnosis. The aim of this study was to review current knowledge regarding the current methods of diagnosis and treatment of gastric metastasis of breast cancer. Methods: A systematic literature search was performed in the Pub-Med Medline database using the terms "gastric metastasis of lobular breast cancer" and "gastric metastasis features" to identify articles relevant to gastric metastasis of lobular breast cancer. Results: Several papers have shown that the topic is rarely presented in the form of case presentations or miniseries by summing up sporadic cases. Due to its rarity and metastasis specificity as host type and appearance after latency of lobular breast cancer makes its gastric metastasis considered atypical and occasionally confused with a primary stomach malignancy. The most recent articles present the immunohistochemical diagnostic criteria of this clinical entity and a new therapeutic approach. Conclusion: At patients with gastric metastasis of lobular breast cancer, obtaining pathologic material and biopsies interpretation can be a real challenge for getting a correct pathologic diagnosis, immunohistochemistry gives us definite diagnosis. The introduction of an endoscopic surveillance protocol for patients with lobular breast cancer could be a proposal for the detection of early gastric metastases allowing for appropriate therapy.

Postoperative Esophageal Leaks in Malignant Pathology - Optimal Management: A Systematic Review.

BACKGROUND AND AIMS: Postoperative esophageal leaks are one of the major causes of postoperative mortality and morbidity. The purpose of this study was to review current knowledge of current methods of diagnosis and management of postoperative esophageal leaks. Methods: A systematic literature search was performed in the PubMed/Medline database using the terms "postoperative esophageal leaks" and "postesophagectomy complications" to identify articles relevant to the current diagnostic and prophylactic and curative treatment of post-oesophagectomy anastomotic fistulas. Results: Several papers have shown that the incidence of fistulas varies and is dependent on several factors: the location of the anastomosis, the type of suture used, the biological condition of the patient. Due to the severity of the mediastinal anastomotic fistula, great importance is being given to the methods of preventing its occurrence by intraoperative testing or improving the gastric tube vascularity. The most recent articles present endoscopic methods of treating this complication by using coated esophageal stents and endoluminal vacuum therapy. CONCLUSION: In patients with mediastinal postoperative esophageal fistulas, diagnosis and management represent a real challenge for the surgeon-endoscopist-therapist team. The early diagnosis and the establishment of an optimal therapy to address the parietal defect and the biological status of the patient are mandatory conditions for resolving this postoperative complication.

Implementation of an acute DVT ambulatory care pathway in a large urban centre: current challenges and future opportunities.

BACKGROUND: Ambulatory management of isolated acute deep venous thrombosis (DVT) is the recommended standard of care in selected populations. However, in practice a significant number of patients continue to be managed as in-patients. OBJECTIVES: In this study we aimed to evaluate acute DVT treatment pathways in our emergency department (ED) in practice and to identify barriers to outpatient management. METHODS: This study was a cross-sectional analysis of prospectively collected data pertaining to consecutive patients presenting to the ED of a large, city center, academic teaching hospital over a 46 week period who were diagnosed with DVT. RESULTS: Implementation of an outpatient care pathway led to the majority of patients presenting with DVT in our institution being treated without hospital admission. Forty percent (31/78) of patients with DVT were treated with a direct oral anticoagulant (DOAC) as an outpatient in line with international best practice guidelines. CONCLUSION: The study provides a clear picture of the clinical profile and management of patients in clinical practice. Due to the lack of resources and supported infrastructure it is difficult to effectively implement outpatient venous thromboembolism (VTE) management to its full potential. Directing resources towards strategies which facilitate outpatient DVT treatment among vulnerable patient groups could represent a means of reducing hospital admissions for DVT in urban centers. Our study highlights the success and clinical limitations of the outpatient treatment model, which should become standard as part of wider VTE care.

Mechanistic role of cytochrome P450 (CYP)1B1 in oxygen-mediated toxicity in pulmonary cells: A novel target for prevention of hyperoxic lung injury.

Supplemental oxygen, which is routinely administered to preterm infants with pulmonary insufficiency, contributes to bronchopulmonary dysplasia (BPD) in these infants. Hyperoxia also contributes to the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in adults. The mechanisms of oxygen-mediated pulmonary toxicity are not completely understood. Recent studies have suggested an important role for cytochrome P450 (CYP)1A1/1A2 in the protection against hyperoxic lung injury. The role of CYP1B1 in oxygen-mediated pulmonary toxicity has not been studied. In this investigation, we tested the hypothesis that CYP1B1 plays a mechanistic role in oxygen toxicity in pulmonary cells in vitro. In human bronchial epithelial cell line BEAS-2B, hyperoxic treatment for 1-3 days led to decreased cell viability by about 50-80%. Hyperoxic cytotoxicity was accompanied by an increase in levels of reactive oxygen species (ROS) by up to 110%, and an increase of TUNEL-positive cells by up to 4.8-fold. Western blot analysis showed hyperoxia to significantly down-regulate CYP1B1 protein level. Also, there was a decrease of CYP1B1 mRNA by up to 38% and Cyp1b1 promoter activity by up to 65%. On the other hand, CYP1B1 siRNA appeared to rescue the cell viability under hyperoxia stress, and overexpression of CYP1B1 significantly attenuated hyperoxic cytotoxicity after 48 h of incubation. In immortalized lung endothelial cells derived from Cyp1b1-null and wild-type mice, hyperoxia increased caspase 3/7 activities in a time-dependent manner, but endothelial cells lacking the Cyp1b1 gene showed significantly decreased caspase 3/7 activities after 48 and 72 h of incubation, implying that CYP1B1 might promote apoptosis in wild type lung endothelial cells under hyperoxic stress. In conclusion, our results support the hypothesis that CYP1B1 plays a mechanistic role in pulmonary oxygen toxicity, and CYP1B1-mediated apoptosis could be one of the mechanisms of oxygen toxicity. Thus, CYP1B1 could be a novel target for preventative and/or therapeutic interventions against BPD in infants and ALI/ARDS in adults.

KRAS gene mutations - prognostic factor in colorectal cancer?

The colorectal cancer (CRC) modern therapy is using adjuvant and neoadjuvant companion therapeutic agents, part of them having an anti-angiogenic action. Their benefic effect can be annulated by some gene mutations, which are interfering in signal transduction pathways. One of the more frequent activating mutations is occurring in the KRAS gene. We assessed the KRAS mutations by two molecular methods, in a group of patients with a follow-up until 144 months, aiming to establish eventual correlations between the presence of mutations and the evolution of patients. We tried to appreciate the prognostic value of these mutations. A retrospective study was conducted on 74 patients treated by radical surgery; the surgical specimens were analyzed macroscopically and the histopathological type and degree were established. PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and pyrosequencing were performed on paraffin-embedded tumor specimens. Statistical analysis showed significant differences in survival between patients with wild type gene and patients with mutation in codon 13; the same results were also obtained regarding TNM I, II stages or Dukes type A and B cases. However, for the patients in stage IV pTNM, the evolution was slightly better in association with a KRAS mutation than in wild type cases.

Single nucleotide polymorphisms in colorectal cancer: associations with tumor site and TNM stage.

BACKGROUND AND AIM: Colon tumor carcinogenesis and rectal tumor carcinogenesis have each been associated with different genetic features, but data are still controversial and are insufficient to support their distinct molecular biology. Recently, genome-wide association studies (GWAS) have also found heterogeneity in colorectal cancer (CRC) risks based on population ethnicity and tumor features. Several single nucleotide polymorphism (SNP) markers are described in the literature as having site and/or stage specificity, including rs10795668, rs3802842, rs6983267, and rs4939827. Replication of initial findings in different ethnic groups by independent studies is required to unravel the population-specific differences in risk. METHODS: We examined whether inherited risk variants at rs10795668, rs3802842, rs6983267, and rs4939827 exerted a differential effect on colon and rectal cancers in a Romanian hospital based series of 153 CRC cases and 182 non-affected control subjects prospectively recruited between 2007 and 2010. RESULTS: Rectal tumors were significantly associated with rs4939827 (OR = 4.85, P = 0.002) and rs6983267 (OR = 3.00, P = 0.036), suggesting that carriers of risk alleles at these loci had increased susceptibility to development of rectal cancer rather than colon cancer. Carrying the C allele at rs3802842 appeared to be associated with a lower risk for rectal tumors in our dataset. We found no association between genotypes and tumor aggressiveness as reflected by TNM staging. CONCLUSIONS: The associations between SNPs, and tumor site and staging remain to be further clarified. Our results should be considered cautiously, but may be taken into account in future, larger epidemiological studies.

[Features of Krukenberg-type tumors--clinical study and review]. / Particularitati ale tumorilor de tip Krukenberg--studiu clinic si review.

Krukenberg-type tumors (KT) are rare among ovarian metastases, but responsible for the most frequent diagnostic confusions with ovarian cancer. They are peculiar: uncertain pathogenesis, challenging etiological diagnosis, poorer prognosis for the primary. We studied 9 cases, with a mean age of 52 years, operated since 2001; no case was discovered as a result of prophylactic oophorectomy. Timing of TK diagnosis: 3--metachronous, 4--synchronous, as incidental discovery and 2--retrospective pathological diagnosis. Site of primary: 3--gastric, 5--colonic or appendiceal, 1--breast. Imaging appearance was useful only if interpreted in clinical conditions. Morphology: 7/9 bilateral, solid or mixed gross appearance, oval, mean diameters 9.4/7.8 cm. Microscopy: in 8 KT of digestive origin, 3--signet-ring cell carcinoma, 3--mucinous adenocarcinoma, 2--mixed pattern; 1 KT or breast origin was diagnosed by immunohistochemistry; 6/9 presented microscopic peritoneal despite a lack of strong correlation with the appearance of carcinomatosis or cytology of ascites. Survival: 3--no evidence, 5--disease-free after 4-13 months, 1--survived 2 years after debulking (4 years after colectomy). Clinical, evolutive and prognostic features of KT are determined by the biologically behavior of the primary (rapid lymphatic and hematogenous spread to the ovary), so the benefit of surgery is limited. Bilateral ovarian tumors, particularly in premenopausal women, must raise a high index of suspicion for KT, before or during surgery; diagnosis is a team challenge.

Pseudo-achalasic behaviour of a middle thoracic esophageal squamous cell carcinoma.

Pseudo-achalasia is a rare pathologic entity that mimics idiopathic achalasia, usually secondary to malignant infiltration of the cardia. Its significance is related to the fact that it may be difficult to distinguish from primary achalasia; the outcome and therapeutic course are different. In fact, a large variety of processes may be responsible for the development of a secondary achalasia syndrome; we present a case with pseudo-achalasia due to a middle thoracic esophageal squamous cell carcinoma.

[Simultaneous bilateral breast carcinoma--case study and review of primitive bilateral breast cancer]. / Carcinom mamar bilateral, simultan. Studiu de caz si review asupra cancerului mamar bilateral primitiv.

Bilateral breast cancer is uncommon and difficult to define because it may manifest as simultaneous, synchronous or metachronous tumours. The true clonal origin and biologic behaviour are still controversial. Following a right breast contusion, bilateral breast tumours were diagnosed in a 74 old female patient; the left one, neglected for 3 years, typically scirrous; the right one with cystic, pseudo-inflammatory appearance. Sonography and fine-needle cytology concluded: left, carcinoma (T3bN1Mx); right, benign nodule with traumatic hematoma. Three sessions of chemotherapy were followed by simultaneous left Madden mastectomy and right simple mastectomy (frozen sections negative for malignancy). Histopathology: left, invasive lobular carcinoma (ypT4N0Mx); right, micropapillary invasive carcinoma mixed with adenoid cystic carcinoma. After another 3 chemotherapeutic sessions, right axillary lymphadenectomy was performed. Both lesions were evaluated by immunohistochemistry and the TNM pathological classification was reconsidered; left, ypT4N1Mx; right, ypT3N0Mx. Considering the natural history, histopathological and immunohistochemical patterns of the two tumours, these seem to be distinct but shearing a common favourable biologic behaviour. No genetic studies were performed in the absence of specific risk factors. Based on clinical, epidemiologic, morphologic and genetic evidence, bilateral breast cancers (synchronous or metachronous) are considered to be a special evolutive entity of breast cancer. Our case suggests that, in the absence of risk factors for bilaterality of breast carcinoma: description of bilateral breast cancers based on diagnostic chronology of the two tumours is arbitrary; they may occur sporadically and have independent evolution; their biology rather resembles a multiple primitive malignancy than a true bilateral breast cancer.

[Ectopic intestinal varices in cirrhotic patients; an infrequent cause of severe intestinal bleeding]. / Varice ectopic intestinal la bolnavul cirotic; cauza rara de hemoragie digestiva inferioara acuta.

We report on a cirrhotic patient, with history of colecistectomy, admitted for acute digestive bleeding. Esogastric causes were excluded by endoscopy; due to continuous hemorrhage, the patient was operated in the next 20 hours. The cause was established during the operation; solitary omfalo-enteric varices, with active vascular fistula. Preoperative etiology of acute intestinal bleeding may be difficult to establish, sometimes even during the surgical intervention. We comment upon rare causes of acute intestinal bleeding, mainly ectopic varices determined by portal hypertension.

[Osteo-articular manifestations after suppurative pancreatitis]. / Manifestari osteo-articulare consecutive supuratiei pancreatice acute prelungite.

Osseous and joint manifestations (decalcification, osteolysis, osteonecrosis; poliarthrytis; periarticular fat necrosis) are sometimes encountered in chronic pancreatitis or carcinoma, but exceptional after severe acute pancreatitis, especially infected pancreatic necrosis. Pathogenesis of calcium deficiency in acute pancreatitis is multifactorial, including extensive lipolysis and metabolic disturbances. We report on a healthy, young male, that developed decalcification and polyarthritis consecutive to a long-outcome, severe acute pancreatitis. We comment upon hypocalcemia, as a rare complication of acute pancreatitis.

[Infiltrating mucinous carcinoma developed on chronic anal fistula; diagnostic and surgical difficulties]. / Carcinom coloid infiltrativ grefat pe supuratie cronica ano-rectala; dificultati de diagnostic si tratament chirurgical.

Anal carcinoma is rare; fistula-in-ano is sometimes mentioned among other premalignant conditions. Chronic anal fistula is associated with malignant transformation to mucinous adenocarcinoma, difficult to diagnose in the anal region and associated to a poor prognosis. Malignant transformation to infiltrating colloid carcinoma was surprised during a one year period, in a patient with long-standing perianal fistula (24 years). Inflammatory changes of the perineal region and other peculiar characteristics (such as neoplastic spread following supurative pathways) were responsible for diagnostic and surgical difficulties.