MEN2 phenotype in a family with germline heterozygous rare RET K666N variant.

Summary: Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by germline-activating pathogenic variants in the RET proto-oncogene. MEN2A is the most common subtype, with a risk for medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT), whereas MEN2B is less common and associated with MTC and PHEO along with mucosal neuromas. Little is known about the specific RET germline heterozygous variant K666N. This variant has been described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. There is one case of MTC and bilateral PHEO. The RET K666N variant is not stratified yet by the American Thyroid Association, and data are limited on pathogenicity; therefore, appropriate screening and treatment of asymptomatic RET K666N carriers are unclear. Here, we report a family with a heterozygous germline RET K666N variant. The proband was identified when she experienced cardiogenic shock and multi-organ failure after an elective hysterectomy and subsequently was found to have PHEO, with genetic testing revealing the RET K666N germline variant. Patient consent was obtained through IRB protocol COMIRB #15-0516. Learning Points: The specific RET germline heterozygous variant K666N is rare and described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. Our proband is much younger and has PHEO, MTC, and PHPT. The RET K666N germline variant appears to be a low penetrance variant for MEN2.

Acute intestinal ischemia in patients with COVID-19: single-centre experience and literature review.

OBJECTIVE: Acute Intestinal ischemia (AII) may involve the small and/or large bowel after any process affecting intestinal blood flow. COVID-19-related gastrointestinal manifestations, including AII, have been attributed to pharmacologic effects, metabolic disorders in ICU patients and other opportunistic colonic pathogens. AII in COVID-19 patients may be due also to "viral enteropathy" and  SARS-CoV-2-induced small vessel thrombosis. A critical appraisal of personal experience regarding COVID-19 and AII was carried out comparing this with a systematic literature review of published series. PATIENTS AND METHODS:   A retrospective observational clinical cohort study and a systematic literature review including only COVID-19 positive patients with acute arterial or venous intestinal ischemia were performed. The primary endpoint of the study was the mortality rate. Secondary endpoints were occurrence of major complications and length of hospital stay. RESULTS: Patient mean age was 62.9±14.9, with a prevalence of male gender (23 male, 72% vs. 9 female, 28%). The mean Charlson Comorbidity Index was 3.1±2.7. Surgery was performed in 24/32 patients (75.0%), with a mean delay time from admission to surgery of 6.0 ±5.6 days. Small bowel ischemia was confirmed to be the most common finding at surgical exploration (22/24, 91.7%). Acute abdomen at admission to the ED (Group 1) was observed in 10 (31.2%) cases, while 16 (50%) patients developed an acute abdomen condition during hospitalization (Group 2) for SARS-CoV-2 infection. CONCLUSIONS: Our literature review showed how intestinal ischemia in patients with SARS-CoV-2 has been reported all over the world. The majority of the patients have a high CCI with multiple comorbidities, above all hypertension and cardiovascular disease. GI symptoms were not always present at the admission. A high level of suspicion for intestinal ischemia should be maintained in COVID-19 patients presenting with GI symptoms or with incremental abdominal pain. Nevertheless, a prompt thromboelastogram and laboratory test may confirm the need of improving and fastening the use of anticoagulants and trigger an extended indication for early abdominal CECT in patients with suggestive symptoms or biochemical markers of intestinal ischemia.

Management of Small Bowel Obstruction (SBO) in older adults (>80 years): a propensity score-matched analysis on predictive factors for a (un)successful non-operative management (NOM).

OBJECTIVE: Small Bowel Obstruction (SBO) is a common emergency in older patients. The most appropriate treatment strategy is still matter of debate. The aim of this study was to compare a non-operative management (NOM) vs. a surgical procedure for patients ≥ 80 years with SBO. PATIENTS AND METHODS: All patients ≥ 80 years admitted to our Emergency Department (ED) for SBO between January 1st, 2015, and December 31st, 2020 were included in this study. In order to correct for baseline covariates and factors associated to clinical management, we used a 1:1 propensity score matching (PSM) analysis. The primary outcome was to compare the overall in-hospital mortality. Secondary outcomes included occurrence of major complications and in-hospital length of stay (LOS). RESULTS: A total of 561 patients were enrolled. After propensity score matching (PSM) analysis, 302 patients (151 each group) were included in the analysis. Mortality did not differ between the two groups. After PSM mechanical ventilation, sepsis, cumulative major complications, and LOS were significantly higher in the operative treatment group [15.9% vs. 1.5%, 9.4% vs. 4.1%, 27.6% vs. 19.2%, and 9.4 (6.4-14.3) days vs. 8.1 (4.5-13.3) days, respectively; p<0.001, p=0.013, p=0.025, and p=0.003, respectively]. CONCLUSIONS: In patients ≥ 80 years with SBO, a NOM could yield similar results, in terms of overall mortality, compared to a surgical management. Thus, particularly in patients with multiple comorbidities or functional impairments, a conservative approach should always be considered.

Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT.

Epithelial to mesenchymal transition (EMT) is a critical cellular process that has been well characterized during embryonic development and cancer metastasis and it also is implicated in several physiological and pathological events including embryonic stem cell differentiation. During early stages of differentiation, human embryonic stem cells pass through EMT where deeper morphological, molecular and biochemical changes occur. Though initially considered as a decision between two states, EMT process is now regarded as a fluid transition where cells exist on a spectrum of intermediate states. In this work, using a CRISPR interference system in human embryonic stem cells, we describe a molecular characterization of the effects of downregulation of E-cadherin, one of the main initiation events of EMT, as a unique start signal. Our results suggest that the decrease and delocalization of E-cadherin causes an incomplete EMT where cells retain their undifferentiated state while expressing several characteristics of a mesenchymal-like phenotype. Namely, we found that E-cadherin downregulation induces SNAI1 and SNAI2 upregulation, promotes MALAT1 and LINC-ROR downregulation, modulates the expression of tight junction occludin 1 and gap junction connexin 43, increases human embryonic stem cells migratory capacity and delocalize ß-catenin. Altogether, we believe our results provide a useful tool to model the molecular events of an unstable intermediate state and further identify multiple layers of molecular changes that occur during partial EMT.

Bushfire impact on youth.

The authors examined the association between disaster-related traumatic experiences and posttraumatic stress disorder (PTSD) symptoms in 155 youth, aged 8-18 years, from the Lower Eyre Peninsula of South Australia who were affected by January 2005 bushfires. Youth completed measures of PTSD symptoms and disaster experiences 11-5 months postdisaster. Many youth (27%) reported moderate to severe levels of PTSD symptoms; younger children reported greater PTSD symptom severity than older youth. Perceived personal life threat and ongoing loss/disruption were related to greater PTSD symptomatology. Following disasters, it may be helpful to identify young children and youth who perceived that their life was threatened and experienced more ongoing life disruption, as these youth may be at higher risk for persistent PTSD symptoms.

Duodenal perforation in a SARS-CoV-2-positive patient with negative PCR results for SARS-CoV-2 in the peritoneal fluid.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has significantly affected health care organizations globally. Many aspects of this disease, as well as the risks for patients treated with multiple drug regimens to control severe COVID-19, are unclear. During emergency surgery for SARS-CoV-2-positive patients, the risk of SARS-CoV-2 exposure and transmission to the surgical staff has yet to be determined. PATIENTS AND METHODS: In this report, we describe a SARS-CoV-2-positive patient with severe respiratory syndrome treated with multiple doses of IL-6 inhibitors who presented with a perforated duodenal ulcer and underwent emergency surgery. During and after surgery, we tested for SARS-CoV-2 at the ulcer site and in the peritoneal fluid. RESULTS: The history of the patient allows for two possible interpretations of the pathogenesis of the duodenal ulcer, which could have been a stress ulcer, or a gastrointestinal ulcer associated to the use of IL-6 inhibitors. We also noticed that the ulcer site and peritoneal fluid repeatedly tested negative for SARS-CoV-2. Therefore, we reviewed the pertinent literature on gastrointestinal bleeding in patients with COVID-19 and on SARS-CoV-2 detection in the peritoneal fluid of surgical patients and discussed possible prevention strategies for bleeding and the actual risk of infection for the surgical staff. CONCLUSIONS: The first implication of this case is that the relation between repeated administration of IL-6 inhibitors and upper gastrointestinal bleeding and perforation must be investigated, and that the threshold for administering prophylactic proton pump inhibitors therapy should be carefully considered for patients with severe COVID-19. The second implication is that further testing should be performed on the peritoneal fluid of COVID-19 patients undergoing emergency surgical procedures to clarify the discordant results for the presence of SARS-CoV-2 in the peritoneal cavity and the possible risk of transmission to the surgical staff.

Percutaneous cholecystostomy in the treatment of acute cholecystitis: is there still a role? A 20-year literature review.

OBJECTIVE: Percutaneous cholecystostomy (PC) is used for the treatment of acute cholecystitis in patients with high surgical risk due to the severity of cholecystitis and/or the underlying acute or chronic medical comorbidities. The evidence for this strategy is unclear. MATERIALS AND METHODS: We searched PubMed and the Cochrane databases for English-language studies published from January 1979 through December 31, 2019, for randomized clinical trials (RCTs), meta-analyses, systematic reviews, and observational studies. RESULTS: The two randomized studies that have compared PC with cholecystectomy (CCY) or conservative treatment have shown that the clinical outcomes did not differ significantly between the groups. Similar results have been found in the large majority of retrospective cohorts or single-center studies that have compared PC with CCY. CONCLUSIONS: PC does not seem to offer any benefit compared with CCY in the treatment of acute cholecystitis in patients with high surgical risk due to the severity of cholecystitis and/or the underlying acute or chronic medical comorbidities. A large, prospective, randomized study that compares percutaneous PC and CCY in patients with high surgical risk and/or moderate to severe cholecystitis is warranted.

Negative pressure wound therapy (NPWT) in duodenal breakdown fistulas: negative pressure fistula therapy (NPFT)?

OBJECTIVE: To describe for the first time in literature the specific methodology of use of negative pressure wound therapy (NPWT) for duodenal fistula through clinical cases. The constant increase of use of NPWT for complex surgical situations imposes tailored previously undescribed solutions for the technique. PATIENTS AND METHODS: Herein, three cases of high output duodenal fistula successfully treated with Negative Pressure Wound Therapy (NPWT) are reported. The technical details for the application of NPWT to these fistulas are discussed and described. RESULTS: All three patients recovered without the necessity of further surgical operations. CONCLUSIONS: When using NPWT, management of high-output duodenal fistulas must rely on some degree of customization of the aspiration systems. The aim of the procedure is to put under depression the duodenal hole and surrounding tissues "all in one" and not to separate the complex wound in sectors as usually indicated. We suggest calling this technique Negative Pressure Fistula Therapy.

Comparison of cholecystectomy and percutaneous cholecystostomy in acute cholecystitis: results of a retrospective study.

OBJECTIVE: To retrospectively compare the clinical outcomes of percutaneous cholecystostomy (PC) and cholecystectomy in patients with acute cholecystitis admitted to an urban University Hospital. PATIENTS AND METHODS: We studied 646 patients with acute cholecystitis. Ninety patients had placement of a PC at their index hospitalization, and 556 underwent cholecystectomy. Of the 90 patients with PC, 13 underwent subsequent elective cholecystectomy. RESULTS: Overall, in-hospital mortality and postoperative complications were significantly higher in patients who received PC than in those who underwent cholecystectomy. In the ASA score 1-2 group, patients with PC were significantly older and had a longer postoperative stay while their mortality and morbidity were similar to patients who underwent cholecystectomy. In patients with ASA score of 3, PC and cholecystectomy did not differ significantly for demographic variables and clinical outcomes such as hospital stay, in-hospital mortality, postoperative complications and distribution of complications according to the classification of Clavien-Dildo. In mild, moderate, and severe cholecystitis, patients who underwent PC were significantly older than those who received cholecystectomy. In general, in mild, moderate and severe cholecystitis, the clinical outcomes did not differ significantly between patients who received PC and cholecystectomy. Morbidity was higher in patients with mild cholecystitis who underwent PC. Of the 77 patients dismissed from the hospital with drainage, 12 (15.6%) developed biliary complications and 5 needed substitutions of the drainage itself. CONCLUSIONS: PC does not offer advantages compared to cholecystectomy in the treatment of acute cholecystitis. Its routine use is therefore questioned. There is need of an adequate, randomized study that compares PC and cholecystectomy in high-risk patients with moderate-severe cholecystitis.

Children's predisaster functioning as a predictor of posttraumatic stress following Hurricane Andrew.

This study examined (a) children's predisaster behavioral and academic functioning as a predictor of posttraumatic stress (PTS) following Hurricane Andrew and (b) whether children who were exposed to the disaster would display a worsening of prior functioning. Fifteen months before the disaster, 92 4th through 6th graders provided self-reports of anxiety; peers and teachers rated behavior problems (anxiety, inattention, and conduct) and academic skills. Measures were repeated 3 months postdisaster; children also reported PTS symptoms and hurricane-related experiences (i.e., exposure). PTS symptoms were again assessed 7 months postdisaster. At 3 months postdisaster, children's exposure to the disaster, as well as predisaster ratings of anxiety, inattention, and academic skills, predicted PTS symptoms. By 7 months, only exposure, African American ethnicity, and predisaster anxiety predicted PTS. Prior anxiety levels also worsened as a result of exposure to the disaster. The findings have implications for identifying and treating children at risk for stress reactions following a catastrophic disaster.

Symptoms of posttraumatic stress in children after Hurricane Andrew: a prospective study.

The authors examined symptoms of posttraumatic stress in 3rd-5th grade children during the school year after Hurricane Andrew. From a conceptual model of the effects of traumatic events, 442 children were evaluated 3, 7, and 10 months postdisaster with respect to (a) their exposure to traumatic events during and after the disaster, (b) their preexisting demographic characteristics, (c) the occurrence of major life stressors, (d) the availability of social support, and (e) the type of coping strategies used to cope with disaster-related distress. Although symptoms of posttraumatic stress disorder (PTSD) declined over time, a substantial level of symptomatology was observed up to 10 months after the disease. All 5 factors in the conceptual model were predictive of children's PTSD symptoms 7 and 10 months postdisaster. Findings are discussed in terms of the potential utility of the model for organizing thinking about factors that predict the emergence and persistence of PTSD symptoms in children.

Prediction of posttraumatic stress symptoms in children after hurricane Andrew.

The authors used an integrative conceptual model to examine the emergence of posttraumatic stress disorder (PTSD) symptoms in 568 elementary school-age children 3 months after Hurricane Andrew. The model included 4 primary factors: Exposure to Traumatic Events, Child Characteristics, Access to Social Support, and Children's Coping. Overall, 62% of the variance in children's self-reported PTSD symptoms was accounted for by the 4 primary factors, and each factor improved overall prediction of symptoms when entered in the analyses in the order specified by the conceptual model. The findings suggest that the conceptual model may be helpful to organize research and intervention efforts in the wake of natural disasters.

The relative deprivation of U.S. elderly households as judged by their housing problems.

A substantial number of U.S. elderly households have excessive housing costs or live in physically deficient dwellings. It is unclear, however, whether they are more likely than nonelderly households to experience these housing problems. Using American Housing Survey data, this study investigates whether elderly households are more likely than nonelderly households to have these problems after controlling for their owner-renter status, race, and income. The findings do not support the more deprived housing status of elderly households.

Diagnostic laparoscopy in a HIV positive patient with disseminated non-Hodgkin's lymphoma.

We report a case of massive peritoneal involvement in AIDS-related non-Hodgkin's lymphoma (NHL). Abdominal CT scan showed a retroperitoneal lymphoadenopaty and a wide thickening of omental peritoneum. At laparoscopy a diffuse massive involvement of peritoneum mimicking carcinomatosis was demonstrated and an omentum biopsy revealed a diffuse infiltration of large cell NHL.

Radiofrequency thermal ablation (RFA) of liver tumors: open surgical or percutaneous approach?

RFA was used to ablate 81 liver lesions: 61 liver metastases and 20 hepatomas. An open surgical approach was adopted in 19 instances (27.5%), 12 of which were simultaneously treated for associated diseases, and percutaneous treatment was adopted in 50 instances (72.5%). The CT liver control at 6 months showed a complete necrosis in 50 lesions (66.3%). The advantages of the percutaneous approach include less invasiveness, reduced postoperative pain, shorter hospitalization, reduced costs and less discomfort in repeating the procedure. In conclusion, radiofrequency liver nodule ablation could be considered, today, as one of the promising and versatile techniques for loco-regional liver cancer control.

Peer acceptance: the correspondence between children's sociometric scores and teachers' ratings of peer interactions.

In view of the current interest in children's peer relationships and social skills, and the need for valid assessment procedures for children's peer problems, the intent of the present study was to examine the correspondence between peer ratings of acceptance and teacher ratings of a child's social behavior and likability. The 92 children were males and females from the third, fourth, and fifth grades. Classroom teachers rated each of the children on withdrawal, aggressive, and likable behavior using the Pupil Evaluation Inventory. Peer ratings of the child's acceptance in play and work situations were obtained from same-sex classmates. The teacher rating of likability was the best predictor of peer acceptance scores for males; withdrawn behavior was the best predictor of peer acceptance scores for females. Ratings of withdrawn and aggressive behavior contributed to the prediction of peer acceptance scores for males; for females, only withdrawn behavior contributed to the prediction of peer acceptance. In terms of the clinical utility of teacher ratings for assessing children with peer problems, the use of the withdrawn and/or aggressive ratings scales appeared to offer promise as a means of identifying such children. Implications for the area of children's social skills and directions for future research were discussed.

Social anxiety among adolescents: linkages with peer relations and friendships.

This study examined the utility of modifying the Social Anxiety Scale for Children-Revised (SASC-R) for use with adolescents, and examined associations between adolescents' social anxiety (SA) and their peer relations, friendships, and social functioning. Boys (n = 101) and girls (n = 149) in the 10th through 12th grades completed the Social Anxiety Scale for Adolescents (SAS-A) and measures of social support, perceived competence, and number and quality of their best friendships. Factor analysis of the SAS-A confirmed a three-factor structure: Fear of Negative Evaluation, Social Avoidance and Distress in General, and Social Avoidance Specific to New Situations or Unfamiliar Peers. Girls reported more SA than boys, and SA was more strongly linked to girls' social functioning than boys'. Specifically, adolescents with higher levels of SA reported poorer social functioning (less support from classmates, less social acceptance), and girls with higher levels of SA reported fewer friendships, and less intimacy, companionship, and support in their close friendships. These findings extend work on the SASC-R to adolescents, and suggest the importance of SA for understanding the social functioning and close friendships of adolescents, especially girls.

Comprehension of nonverbal communication: a reexamination of the social competencies of learning-disabled children.

This study was designed to determine whether learning-disabled (LD) children differed from nondisabled (NLD) children in their ability to comprehend nonverbal communication when potential attentional differences between the groups were controlled. In addition, the relationship between nonverbal comprehension and social competence was assessed. Thirty LD and 30 NLD boys between 9 and 12 years of age were administered a short form of the Profile of Nonverbal Sensitivity (PONS) to assess nonverbal comprehension; social competence measures included teachers' ratings of aggressive and withdrawn behaviors using the Behavior Problem Checklist, and "blind" judges' ratings of performance on a role-play of friendship-making skills. Under attention-incentive conditions, no performance differences between LD and NLD children were found on the PONS; however, LD children were judged to be more withdrawn and less socially skilled. While PONS scores were not related to other social competence measures, they were associated with academic achievement and IQ. Results emphasize the importance of considering the presence of attentional problems in LD children that may interfere with an accurate assessment of their skills.