Antenatal prediction of fetal macrosomia in pregnancies affected by maternal pre-gestational diabetes.

AIMS: Higher rates of fetal macrosomia may occur in infants of women with pre-gestational diabetes compared with non-diabetic controls. Antenatal predication of fetal macrosomia remains challenging. Ultrasound over-estimated fetal weight could result in over-classification of fetuses as macrosomic with corresponding inappropriate clinical interventions. Previously we had studied a measurement - the anterior abdominal wall measurement (AAW) - to predict fetal macrosomia in fetal estimation of weight. The purpose of the study was to study whether specific third trimester ultrasound measurements with measures of glycaemic control (HbA1c) predicted macrosomia in babies born to women with pre-gestational diabetes. In particular, a new variant of this measurement (fetal anterior abdominal wall thickness (AAW), abdominal circumference (AC) ratio: AAW:AC) was investigated. METHODS: This was a prospective cohort study in a tertiary referral maternity hospital. Serial growth scans including measurement of AAW and AC: AAW ratio was performed at 30, 33- and 36-weeks' gestation. Birth-weight data was collected, and macrosomia was defined as >90th centile based on gestational age and gender of the baby. Serial HbA1c as measured at the first antenatal visit, 14, 20- and 36-weeks' gestation were reported for this study. RESULTS: Of the 416 pregnancies analyzed, mean maternal age was 33.3 years. One in five women were primigravida's. The mean birthweight was 3548 g (+/- 581 g), of which 142 (34%) babies were classified as macrosomic. The median gestational age at delivery was 383 weeks (314 - 402 weeks). There were 37 (9%) babies born preterm at <37 weeks' gestation. Mean AC measurements in fetuses that would be born with macrosomia compared with those with a non-macrosomic birth weight were 282 mm vs. 266 mm at 30 weeks, 318.3 mm vs. 297 mm at 33 weeks and 350 mm vs. 325 mm at 36 weeks' gestation (all p < .001). Mean AAW measurements in macrosomic fetuses compared with normal size fetuses were 3.7 mm vs. 3.3 mm at 30 weeks, 4.9 mm vs 4.3 mm at 33 weeks and 5.9 mm vs. 5.3 mm at 36 weeks' gestation (all p < .001). The mean AC: AAW was 0.01 for both normal and macrosomic fetuses at 30 weeks. There was no clinical or statistical difference in AC:AAW ratios between non-macrosomic and macrosomic infants. Binary logistic regression showed that AC at 36 weeks was most predictive of macrosomia (76.5%), followed by AAW at 30 weeks (68.5%). Using a combination of HbA1c booking, 14, 20, 36 weeks and AAW 30, 33, 36 weeks and AC 30, 33, 36 weeks predicted macrosomia in 80.9%. The ratio of AC: AAW did not act as a useful antenatal clinical predictor of macrosomia at birth. CONCLUSIONS: Abdominal circumference at 36 weeks was the single best predictor of fetal macrosomia. A combined model of HbA1c, AC and AAW was the best antenatal predictor of macrosomia, with intriguing clinical possibilities in the possible prevention of maternal and fetal complications of macrosomia.

COVID-19 infection in patients with intestinal failure: UK experience.

BACKGROUND: The direct effect of the coronavirus disease 2019 (COVID-19) pandemic on patients with intestinal failure (IF) has not been described. METHODS: We conducted a nationwide study of UK IF centers to evaluate the infection rates, presentations, and outcomes in patients with types 2 and 3 IF. RESULTS: A total of 45 patients with IF contracted COVID-19 between March and August 2020; this included 26 of 2191 (1.2%) home parenteral nutrition (HPN)-dependent adults and 19 of 298 (6.4%) adults hospitalized with type 2 IF. The proportion of patients receiving nursing care for HPN administration was higher in those with community-acquired COVID-19 (66.7%) than the proportion in the entire HPN cohort (26.1%; P < .01). Two HPN-dependent and 1 hospitalized patient with type 2 IF died as a direct consequence of the virus (6.7% of 45 patients with types 2 or 3 infected). CONCLUSION: This is the first study to describe the outcomes of COVID-19 in a large cohort of patients requiring long-term PN. Methods to reduce hospital and community nosocomial spread would likely be beneficial.

Crisis Presentations of Children and Adolescents with Neurodevelopmental Disorders.

Aim To inform the development of a care pathway for children and adolescents with neurodevelopmental disorders presenting to Children's Health Ireland (CHI) at Tallaght Emergency Department. Methods A retrospective study of cases with a neurodevelopmental disorder diagnosis (Autism Spectrum Disorder and/or Mild to Profound Intellectual Disability) presenting to the hospital Child Psychiatry services over a six-year period (Jan 2014 - December 2019). Results 72 patients identified, Autism Spectrum Disorder diagnosis most common (N=67, 93%). Nearly half of cases presenting with risk concerns (N= 35, 49%), same day hospital discharge (N = 53, 74%) and inpatient admission (N=19, 29%). Discussion Access to relevant community disability supports is significantly limited in Ireland with a resultant increase in carer stress and crisis presentations to the emergency department for psychosocial and disability related reasons.

Imaging of adult intestinal failure.

Intestinal failure is the inability to maintain adequate nutrition or hydration through the gut. It is caused by a diverse range of benign and malignant aetiologies. Imaging takes a central role in the multidisciplinary assessment of patients with intestinal failure.

Imaging of intestinal transplantation.

Intestinal transplant is considered in a small number of patients with intestinal failure or locally invasive benign abdominal tumours to improve both quality of life and survival. The complexity of the underlying diseases and postoperative findings are reflected in the imaging undertaken to support this patient group. Increasing numbers of patients are undergoing these procedures. Radiologists are increasingly likely to encounter these patients before and after surgery. This article will discuss the imaging findings that may prompt referral for transplantation assessment. It will also describe surgical anatomy and postoperative complications.

Anticancer effects of resveratrol in canine hemangiosarcoma cell lines.

Hemangiosarcoma (HSA) is a highly malignant tumour with aggressive biological behaviour. HSAs are more common in dogs than other domestic animals. The median survival time of dogs with HSA remains short, even with chemotherapy and surgery. Therefore, there is a critical need to improve the adjuvant chemotherapeutic regimens to improve clinical outcomes in dogs with HSA. Resveratrol has been shown to possess strong anti-proliferative and/or pro-apoptotic properties in human cancer cell lines. Nevertheless, the potential anticancer effects of resveratrol have not been reported in canine HSAs. The objective of this study is to determine the growth inhibitory effects of resveratrol in HSA cells when used alone or in combination with doxorubicin, a commonly used chemotherapeutic agent. Frog and DD-1 canine HSA cell lines were treated with varying concentrations of resveratrol with and without doxorubicin. Cell viability was measured by the MTT assay. The expression of apoptotic proteins, activation of p38 mitogen-activated protein kinase (MAPK), AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase 1/2 (ERK1/2) were assessed by western blotting. Similar to human cancer cell lines, resveratrol markedly inhibited the growth and induced apoptosis in both HSA cell lines. Mechanistically, resveratrol activated p38 MAPK, but did not affect the AMPK or the ERK1/2 pathways. Additional experiments showed that resveratrol augmented the growth-inhibitory and apoptotic effects of doxorubicin in both HSA cell lines. These findings suggest that resveratrol has pro-apoptotic effects in canine HSA cells; therefore, its use as a potential adjunct therapy in canine HSA patients warrants further investigation.

Presumed primary immune-mediated neutropenia in 35 dogs: a retrospective study.

OBJECTIVES: To describe, in a cohort of dogs with presumed primary immune-mediated neutropenia, the presenting clinical characteristics, haematology results, bone marrow characteristics, therapies used (drugs and doses), clinical response to treatment, relapse and outcome at six months and one year. METHODS: Multi-institutional recruited retrospective descriptive case series with voluntary submissions. Presumed immune-mediated neutropenia was diagnosed based on a neutrophil concentration <1·5×109 cells/L on a minimum of two complete blood counts, exclusion of other causes of neutropenia based on a diagnostic bone marrow aspirate or biopsy, and exclusion of secondary immune-mediated neutropenia. Dogs meeting these diagnostic criteria between 2006 and 2013, and that had a haematocrit of ≥29% and minimum of two complete blood clounts performed after initiation of therapy, were included. RESULTS: Information on 35 dogs was included. Neutropenia was less than 0·5×109 cells/L in most cases (21 dogs), 0·5 to ·99×109 cells/L in 11, and 1.0 to 1·49×109 cells/L in three. Eight dogs had thrombocytopenia, which was severe (<49·9×109 cells/L) in three. [Correction added on 23 May 2017, after first online publication: the cell numbers were incorrect due to errors in the conversion of cell measurements to international units. The numbers have been corrected throughout the article and Table 2.] Twenty-three dogs had myeloid hyperplasia, 10 dogs had myeloid hypoplasia and two dogs had normal myelopoiesis. Neutropenia resolved in 32 of 33 dogs within two weeks of starting corticosteroid therapy and in all dogs within one month. Relapse of neutropenia occurred in 12 cases within one year. CLINICAL SIGNIFICANCE: Initial response of presumed primary immune-mediated neutropenia cases to corticosteroid therapy can be excellent. Long-term monitoring for relapse is warranted because 34% of cases relapsed during or after taper of immunosuppressive medications.

Adult Intestinal and Multivisceral Transplantation: Experience From a Single Center in the United Kingdom.

Cambridge is one of two designated adult intestinal transplant centers in the United Kingdom and has performed 60 transplants on 54 patients since 2007; 52% of these were undertaken in the last 3 years. This increasing trend is in contrast with that reported worldwide; 27% were small bowel grafts (SBT), 15% modified multivisceral (MMVT), and 58% multivisceral (MVT). Median recipient age was 47 years; the female-to-male ratio was 27/33. Primary diseases included visceral arterial thromboses (17%), Crohn's disease (17%), motility disorders (12%), visceral venous thromboses (12%), familial adenomatous polyposis (FAP)/desmoids (8%), alcoholic cirrhosis (3%), nonalcoholic fatty liver disease (3%), ulcerative colitis (2%), and other (15%). Indications for transplant included intestinal failure-associated liver disease (IFALD) (27%), loss of central venous access (17%), FAP/desmoid disease (5%), extensive portomesenteric venous thrombosis (PMVT) (20%), widespread mesenteric arterial ischemia (WMAI) (13%), re-transplant (8%), and other (10%). Overall 1-year/5-year patient survival rates were 77%/62%. One-year/5-year patient survival rates were 92%/83%, 85%/65%, and 71%/33% for SBT, MMVT, and MVT. One-year/5-year survival rates for patients with IFALD, PMVT, and other indications who underwent MVT were 80%/20%, 65%/55%, and 55%/35%. The greatest proportion of patient deaths occurred during the first year after transplant (50% in year 1, 23% in year 2, 9% in year 3, 5% in year 4, and 14% in year 5), particularly in the MVT group. Referrals to our United Kingdom center are increasing, and the indications for transplant are becoming more diverse. Our patient survival rates remain comparable with figures reported worldwide.

Cytomegalovirus Infection and Rates of Antiviral Resistance Following Intestinal and Multivisceral Transplantation.

BACKGROUND: Cytomegalovirus (CMV) disease is a common and clinically significant complication following intestinal or multivisceral transplantation. CMV disease is more common in cases of serologic mismatch between donor and recipient. Though in some cases it may be asymptomatic, in the immunosuppressed population it often manifests with evidence of systemic infection or end-organ disease. METHODS: We conducted a retrospective review of all patients undergoing intestinal or multivisceral transplantation over 8 years at our institution. RESULTS: Forty-eight transplantations were performed, with 40% of the patients (19/48) having ≥1 episode of CMV viremia, which rose to 90% in the "donor-positive, recipient-negative" (DPRN) serologic mismatch group. The median time to 1st episode following transplantation was 22.3 weeks (range, 1-78) and median duration of each episode was 4.9 weeks (range, 1.6-37.4). Six of the 19 viremic patients (31.6%) developed virologic resistance with 4 of these occurring in the DPRN group. Four of the 6 patients with drug-resistant CMV died with CMV viremia. All patients with drug resistance acquired ganciclovir resistance; these patients were more challenging to manage with second-line toxicity-limited treatments, including foscarnet, cidofovir, and leflunomide. CMV immunoglobulin has been used and we briefly discuss the use of CMV-specific adoptive T-lymphocyte transfer in the management of 1 case. CONCLUSIONS: Post-transplantation CMV disease continues to be challenging to manage, and there is little consensus on optimal management strategies in this patient group, with a significant requirement for novel therapies; these may be pharmacologic or cell based. Extensive multidisciplinary discussion is important for most cases, but particularly for those patients who acquire virologic resistance.

Serum Beta Hydroxybutyrate Concentrations in Cats with Chronic Kidney Disease, Hyperthyroidism, or Hepatic Lipidosis.

BACKGROUND: Ketones, including beta hydroxybutyrate (BHB), are produced in conditions of negative energy balance and decreased glucose utilization. Serum BHB concentrations in cats are poorly characterized in diseases other than diabetes mellitus. HYPOTHESIS: Serum BHB concentrations will be increased in cats with chronic kidney disease (CKD), hyperthyroidism (HT), or hepatic lipidosis (HL). ANIMALS: Twenty-eight client-owned cats with CKD, 34 cats with HT, and 15 cats with HL; 43 healthy cats. METHODS: Prospective observational study. Serum BHB concentrations were measured at admission in cats with CKD, HT, and HL, for comparison with a reference interval established using healthy cats. Results of dipstick urine ketone measurement, when available, were compared to BHB measurement. RESULTS: Beta hydroxybutyrate was above the reference interval (<0.11 mmol/L) in 6/28 cats (21%) with CKD, 7/34 cats (20%) with HT, and 11/15 cats (73%) with HL, significantly exceeding the expected 2.5% above the reference interval for healthy cats (P < .001 for all groups). Elevations were mild in CKD and HT groups (median BHB 0.1 mmol/L for both groups, 80th percentile 0.12 and 0.11 mmol/L, respectively), but more marked in HL cats (median BHB 0.2 mmol/L, 80th percentile 0.84 mmol/L). None of 11 cats with increased serum BHB concentration having urine dipstick analysis performed within 24 h of sampling for BHB were ketonuric. CONCLUSIONS AND CLINICAL IMPORTANCE: Increases in serum BHB concentrations occur in cats with CKD, HT, and HL, and might provide an useful index of catabolism.

Adult small intestinal and multivisceral transplantation: lessons through the "retrospecto-scope" at a single UK centre from 1991 to 2013.

The first intestinal transplantation in the United Kingdom was performed in Cambridge in 1991. Thirty-eight intestinal transplantations have since been performed in 35 patients. All deaths in the first postoperative month related to hemorrhage, in 2 cases to severe portal hypertension (SPH) and poor venous access in 2. We have modified our practice to reduce the bleeding risk with SPH. Loss of venous access can be avoided by timely referral. Rejection was implicated in 3/14 deaths all dying of sepsis. Cytomegalovirus disease resulted in 2 deaths; we try to avoid CMV-positive donors giving to CMV-negative recipients. Three deaths were related to psychiatric illness, which led to loss of graft in 2 others. Three patients were retransplanted (2 rejections and 1 infarction) and all remain alive. Most patients (10/13) experienced a fall in body weight in the first postoperative year after SB/MV transplantation. Body weight fell by as much as 25%. As transplantation resulted in a net gain in small bowel in most cases, the postoperative loss of native body weight may be underestimated. Interestingly this was not associated with a significant fall in midarm circumference or handgrip strength. Long-term nutrition can be maintained with oral intake in the majority of patients post-SBT. There is improvement in handgrip strength post-transplant. Transplantation does not significantly alter weight, albumin, or other common anthropometric markers. Despite these problems, our 5-year survival results remain relatively good at 73% in the cohort from 1991, 79% from 2003, and 80% from 2008. We consider that deployment of strategies learned from our experiences has improved outcomes.

Prothrombotic disorders in a cohort of 25 patients undergoing transplantation: investigation and management implications.

BACKGROUND: Many patients referred for intestinal transplantation have a history of thrombosis. We undertook an analysis of transplanted patients to describe the history and frequency of thrombosis, clinical course, and management strategies used. RESULTS: Twenty-five patients underwent transplantation of intestine containing blocks between 2007 and 2012; 20 of 25 are still alive. Five of 25 patients were transplanted with history of portomesenteric thrombosis, 6 of 25 had experienced loss of venous access due to thrombosis, and 6 of 25 had history of mesenteric ischemia. Pretransplantation, 16 of 25 patients were anticoagulated. Thrombophilia screens identified 3 of 16 patients who were JAK2 positive, 1 of 25 who had antithrombin deficiency, and 1 of 25 who had a factor V Leiden heterozygote. Post-transplantation, of all 16 patients who were anticoagulated pretransplantation and continued postoperatively, 1 of 16 infarcted their small bowel graft and 4 of 16 developed a further venous thrombosis despite anticoagulation. Of the 9 without a previous history of thrombosis, 1 had a pulmonary embolus more than a decade after transplantation and another had an upper limb deep vein thrombosis associated with a line. Both were then anticoagulated. Seven of 25 are not anticoagulated, although they are administered antiplatelet prophylaxis. Postoperative bleeding complications of anticoagulation occurred in 3 patients. After a subarachnoid hemorrhage in 1 of those 3 patients, anticoagulation was stopped. The other 2 patients bled during ileal biopsy, and both remain on low molecular weight heparin treatment. CONCLUSION: Those with identifiable thrombophilic tendency and a history of venous or arterial thrombosis are considered to be at high risk for recurrent thrombosis. Those without such a history could be considered low risk. Our practice is to anticoagulate all high-risk individuals before and after transplantation and offer antiplatelet prophylaxis to low-risk patients as the risk of anticoagulation probably outweighs the risk of thrombosis for them. Early input from hematologists is vital in the management of high-risk patients, particularly those who thrombose when anticoagulated.

Platelet volume and plateletcrit in dogs with presumed primary immune-mediated thrombocytopenia.

BACKGROUND: Mean platelet volume (MPV) and plateletcrit (PCT) are indices used in evaluating immune-mediated thrombocytopenia (IMT) in humans and in dogs with congenital macrothrombocytopenia. These indices may provide clinically valuable information in acquired thrombocytopenia. HYPOTHESIS/OBJECTIVES: Dogs with presumed primary IMT will have increased MPV, and therefore platelet mass (PCT) will increase faster than platelet count (PLT) during recovery. ANIMALS: Forty-nine dogs with automated PLT < 30,000/µL because of presumed primary IMT and hematocrit (HCT), PCT, MPV, and platelet distribution width determined from the same complete blood count (CBC), and 46 healthy controls. METHODS: Case-control retrospective study; PLT, PCT, MPV, and platelet distribution width (PDW) were recorded from CBCs from 49 dogs, with 45 having data collected on the day of presentation. Fifteen were confirmed to have attained a PLT ≥ 75,000/µL on at least 1 CBC within 15 days after admission. The PCT equivalent to a PLT of 75,000/µL (assuming an average MPV) was calculated for comparison with PLT in terms of time to achieve a threshold of platelet mass by the 2 measures. RESULTS: Mean platelet volume was higher in IMT dogs (17.3 fl) than the reference population (10.5 fl) (P < .0001). The PDW was not significantly different among the groups. The median time for PCT to reach threshold in confirmed responders was faster (3 days) compared with PLT (4 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Immune-mediated thrombocytopenia is characterized by increased MPV. Time to achieve a threshold PCT tended to be shorter than PLT, suggesting that PCT may be a useful platelet parameter for monitoring dogs with IMT.