Incidence of congenital complications related to COVID-19 infection during pregnancy.

PURPOSE: Infection with COVID-19 during pregnancy has been associated with a hypercoagulable state. It is unknown if maternal COVID-19 infection results in congenital anomalies secondary to intrauterine vascular accidents. This study sought to determine if the rate of in-utero vascular complications (intestinal atresia and limb abnormalities) that may be attributable to the hypercoagulable states associated with COVID-19 and pregnancy increased after the onset of the pandemic. METHODS: Pregnancy, neonatal, and congenital defect data from a single academic medical center and the partner's children's hospital were collected and compared to the period prior to onset of the pandemic. A subanalysis including pregnant woman 18 years or greater with documented COVID-19 infection during gestation between March 2020-2021 was performed. RESULTS: Rates of intestinal atresia did not differ prior to or after the onset of the pandemic (3.78% vs 7.23%, p = 0.21) nor did rates of limb deficiency disorders (4.41% vs 9.65%, p = 0.09). On subanalysis, there were 194 women with COVID-19 infection included in analysis: 135 (69.6%) were positive during delivery admission and 59 (30.4%) were positive earlier in their pregnancy. There was one infant born with intestinal atresia. CONCLUSION: We report a low incidence of congenital anomalies in infants born to mothers with COVID-19 infection. It remains unclear if the impact of COVID-19 on the coagulative state augments the normal pro-thrombotic state of pregnancy; ongoing surveillance is warranted.

Audit of compliance with the British Committee for Standards in Haematology (BCSH) revised guidelines for the diagnosis and assessment of treatment response of hairy cell leukemia in University Hospital Galway.

INTRODUCTION: Hairy cell leukemia (HCL) is an uncommon B cell lymphoproliferative disorder. The object of the present audit was to assess whether the investigation and management of HCL in University College Hospital Galway (UCHG) complies with the British Committee for Standards in Haematology (BCSH) guidelines. METHODS: Following a review of the records in our Haematology Department, 18 cases of HCL were identified between January 2006 and October 2014. RESULTS: Blood film examination had been performed in all cases. Flow cytometry of liquid material had been undertaken in 89 % (n = 16) of cases, of which only 31 % (n = 5) included all four hairy cell panel markers (CD11c, CD25, CD103, CD123). Although all initial trephine biopsies included CD20, none analyzed DBA44. Only 65 % (n = 11) of treated patients had a post-treatment bone marrow biopsy preformed. CONCLUSION: This audit highlights areas of improvement in the diagnosis and management of HCL in UCHG, which do not currently adhere to the BCSH recommendations.

CD4 T-cell hyporesponsiveness induced by schistosome larvae is not dependent upon eosinophils but may involve connective tissue mast cells.

In areas endemic for schistosomiasis, people can often be in contact with contaminated water resulting in repeated exposures to infective Schistosoma mansoni cercariae. Using a murine model, repeated infections result in IL-10-dependent CD4(+) T-cell hyporesponsiveness in the skin-draining lymph nodes (sdLN), which could be caused by an abundance of eosinophils and connective tissue mast cells at the skin infection site. Here, we show that whilst the absence of eosinophils did not have a significant effect on cytokine production, MHC-II(+) cells were more numerous in the dermal cell exudate population. Nevertheless, the absence of dermal eosinophils did not lead to an increase in the responsiveness of CD4(+) T cells in the sdLN, revealing that eosinophils in repeatedly exposed skin did not impact on the development of CD4(+) T-cell hyporesponsiveness. On the other hand, the absence of connective tissue mast cells led to a reduction in dermal IL-10 and to an increase in the number of MHC-II(+) cells infiltrating the skin. There was also a small but significant alleviation of hyporesponsiveness in the sdLN, suggesting that mast cells may have a role in regulating immune responses after repeated exposures of the skin to S. mansoni cercariae.

Refinement of the genetics of the host response to Salmonella infection in MOLF/Ei: regulation of type 1 IFN and TRP3 pathways by Ity2.

Typhoid fever, which is caused by Salmonella typhi and paratyphi, is a severe systemic disease that remains a major public health issue in several areas of the world. We can model the human disease using mice infected with a related bacterium, Salmonella typhimurium. This model recapitulates several clinical aspects of the human disease and allows for the study of the host response to Salmonella typhimurium infection in vivo. Previous work in our laboratory has identified three Immunity to typhimurium loci (Ity, Ity2 and Ity3) in the wild-derived MOLF/Ei mice, influencing survival after infection with Salmonella typhimurium. The MOLF/Ei alleles at Ity and Ity2 are protective, while the MOLF/Ei allele at Ity3 confers susceptibility. In this paper, we have generated a novel cross combination between the highly susceptible strain, MOLF/Ei, and the resistant strain, 129S6, to better define the genetic architecture of susceptibility to infection in MOLF/Ei. Using this cross, we have replicated the locus on chr 11 (Ity2) and identified a novel locus on chr 13 (Ity13). Using microarrays and transcriptional profiling, we examined the response of uninfected and infected Ity2 congenic mice. These analyses demonstrate a role for both type-1-interferon (IFN) and TRP53 signaling in the pathogenesis of Salmonella infection.

An unusual case of pneumocephalus.

The authors present an unusual cause of pneumocephalus in a previously fit and well female octogenarian who presented with acute onset altered level of consciousness and generalised weakness. Radiological imaging demonstrated widespread cerebritis with pneumocephalus and gas within the superior sagittal sinus. Blood culture grew Clostridium septicum, a virulent but rare organism that can infect normal tissues. The close association between C septicum and both haematological and bowel malignancies must be considered if this organism is cultured.

Successful allogeneic hematopoietic stem cell transplantation for acute myelogenous leukemia in a patient with hepatic echinococcal cyst managed by delayed hepatectomy.

We report the case of a patient who underwent cytotoxic chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia in the presence of hepatic cystic echinococcal infection. The presence of Echinococcus granulosus infection in an immunocompromised host is extremely rare, with lack of established data regarding optimal management. Successful management of the patient's disease processes required a multidisciplinary approach, which included systemic chemotherapy, HSCT, treatment of chronic graft-versus-host-disease, and elective en bloc resection of the hepatic cyst.

Race and ethnicity correlate with survival in patients with gastric adenocarcinoma.

BACKGROUND: Asian centers have consistently reported superior gastric cancer outcomes. Our study examines gastric cancer survival among different races and ethnicities in a large, heterogeneous USA population. PATIENTS AND METHODS: Patients with gastric adenocarcinoma treated in Los Angeles County from 1988 to 2006 were identified from the Los Angeles County Cancer Surveillance Program. Patients were categorized by race and ethnicity as White, Asian, Hispanic and Black. RESULTS: Of 13 084 patients, 39% were White, 22% Asian, 28% Hispanic, 11% Black and 2% other. Asian patients demonstrated higher survival than Whites, Hispanics and Blacks [median survival (MS) 16.3 versus 8.4, 8.7 and 7.9 months, respectively; log-rank P values < 0.001]. Multivariate Cox regression analysis showed that Asians had improved probability of survival [hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.72-0.82; P < 0.001]. In patients who underwent curative-intent surgery, Asian patients demonstrated higher survival than Whites, Hispanics and Blacks (MS 32.7 versus 18.8, 19.9 and 18.9 months, respectively; log-rank P values < 0.001). Multivariate Cox regression analysis showed that Asians had improved probability of survival after surgery (HR 0.79, 95% CI 0.71-0.88; P < 0.001). CONCLUSIONS: Asians with gastric adenocarcinoma have superior outcomes in Los Angeles County. These outcomes verify disparities in gastric cancer survival among different races and ethnicities independent of established clinical and pathologic factors.

Raised troponin T and echocardiographic abnormalities after prolonged strenuous exercise--the Australian Ironman Triathlon.

BACKGROUND: There is concern about whether cardiac damage occurs as a result of prolonged strenuous exercise. OBJECTIVE: To investigate whether competing in a triathlon is associated with cardiac damage based on a sustained increase in cardiac troponin T (cTnT), and whether such an increase correlates with echocardiographic changes METHODS: cTnT and echocardiographic measurements were made in 38 participants in the 2001 Australian ironman triathlon. cTnT was measured the day before, immediately after, and the day following the race. Echocardiography was done the day before, immediately after, and two to six weeks later for measurement of ejection fraction, stroke volume, cardiac output, wall motion analysis, and global left ventricular function (LVF). RESULTS: No subject had detectable cTnT in the pre-race sample. Following the race, 32 subjects (86.5%) had detectable levels of cTnT (>0.01 ng/ml), with six (16.2%) having >0.10 ng/ml. The day after the race, nine subjects (23.7%) still had detectable cTnT, with two recording a level >0.10 ng/ml. Previously described echocardiographic changes of "cardiac fatigue" were observed in the whole cohort. There was a modest but significant correlation between change in ejection fraction and peak cTnT level (p = 0.02, r = 0.39). Athletes with a post-race cTnT >0.10 ng/ml had a greater decrease in global LVF (p = 0.02) and a trend toward a greater fall in ejection fraction and stroke volume than athletes with cTnT levels <0.10 ng/ml. Cardiac output fell in the group with cTnT >0.10 ng/ml (p>0.05). CONCLUSIONS: Participation in ironman triathlon often resulted in persistently raised cTnT levels, and the troponin rise was associated with echocardiographic evidence of abnormal left ventricular function. The clinical significance and long term sequelae of such damage remains to be determined.

Ultrasonography and abdominal radiography versus intravenous urography in investigation of urinary tract infection in men: prospective incident cohort study.

OBJECTIVES: To compare ultrasonography and abdominal radiography with intravenous urography in the investigation of urinary tract infection in men. DESIGN: Prospective study in two hospital departments. Radiological procedures and urological assessments performed on different days by different clinicians SETTING: District general hospital. PARTICIPANTS: Consecutive series of men (n=114) referred to the department of urology for investigation of proved urinary tract infection. INTERVENTIONS: Ultrasonography and intravenous urography of renal tract and assessment of urinary flow rate. Clinical assessment, cystoscopy, urodynamic studies, and transrectal ultrasonography with biopsy. MAIN OUTCOME MEASURES: Sensitivity and specificity of ultrasonography and abdominal radiography compared with intravenous urography. RESULTS: Important abnormalities were seen in 53 of 100 fully evaluated patients, the most common being a poorly emptying bladder (34). The combination of plain radiographs of kidneys, ureter, and bladder and ultrasonography detected more abnormalities than intravenous urography alone. No important abnormality was missed by this combination (sensitivity 100% and specificity 93%). CONCLUSIONS: Ultrasonography with abdominal radiography is as accurate as intravenous urography in detecting important urological abnormalities in men presenting with urinary tract infection. This combination is safer than intravenous urography and should be the initial investigation for such patients. Additional determination of urinary flow rate is useful for the assessment of an incompletely emptying bladder.

Negative inotropic effects of isoprenaline on isolated left atrial assays from aged transgenic mice with cardiac over-expression of human beta(2)-adrenoceptors.

The action of isoprenaline has been evaluated in an isolated, left atrial assay, from aged transgenic mice with cardiac-specific over-expression of the beta(2)-adrenoceptor. In the assay, isoprenaline produced a negative inotropic concentration-response curve that was not altered by incubation with CGP-20712A (1 microM), a beta(1)-adrenoceptor antagonist. However, after incubation with ICI-118,551 (300 nM), a selective beta(2)-adrenoceptor antagonist, isoprenaline produced a positive inotropic concentration-effect curve that was located to the left of the negative inotropic curve. This suggests that the negative inotropic effect was mediated by a homogenous population of negatively-coupled beta(2)-adrenoceptors. In the presence of CGP-20712A (300 nM), the positive curve was shifted to the right, suggesting that the positive inotropic effect was mediated, at least in part, by beta(1)-adrenoceptors. These results differ substantially from those previously obtained in young transgenic mice. An outline of an explanatory model, based on a concept of over-expressed receptors 'stealing' G-proteins, is suggested.

Glucose production by the human placenta in vivo.

The human placenta transports glucose by facilitated diffusion down a concentration gradient from mother to fetus. It has previously been considered incapable of glucose synthesis. However, recent work has demonstrated the presence in placental tissue of glucose-6-phosphatase, which is required for the final step in the synthesis of glucose. Following continuous intravenous infusion into the maternal circulation of the stable isotope, 6,6-(2)H(2)glucose, during elective caesarean section, we have observed isotope dilution in the umbilical vein, without further dilution in the umbilical artery. Using a mathematical model containing maternal, placental and fetal compartments, the data were compatible with the release of glucose by the placenta. We conclude that the human placenta at term can produce glucose.

The check X-ray: an unnecessary investigation after hip fracture fixation?

An X-ray-based image intensification system is a necessary operative aid in many orthopaedic procedures. Technological advances have not only increased the resolution of these systems, but allow the production of thermal images. We have compared such images obtained at the time of surgery with postoperative radiographs in 80 patients who underwent closed reduction and internal fixation for proximal femoral fractures. The films were independently assessed with particular reference to fracture reduction and the adequacy of fixation. In no case did the postoperative radiograph provide additional information. We therefore suggest that a postoperative radiograph is only necessary in exceptional circumstances. This is of significance in relation to patient discomfort, morbidity and radiation exposure. It also has important financial and manpower implications.

Arteriovenous fistula after fibular osteotomy leading to recurrent haemarthroses in a total knee replacement.

We present a patient with an arteriovenous fistula of the peroneal artery acquired after a left dome tibial osteotomy with midshaft fibular osteotomy. He had subsequently had a total knee replacement on that side. The arteriovenous malformation was only diagnosed when he represented with symptoms and signs of venous hypertension with sterile recurrent haemarthroses in the left knee. Percutaneous obliteration of the fistula, by a combination of coil embolisation and balloon occlusion, cured the symptoms.

The relationship of blood glucose and haemoglobin A1 levels in diabetic subjects.

Recommendations exist that fasting plasma glucose (FPG) levels can be substituted for glycosylated haemoglobin A1 (HbA1) in Type II diabetic subjects (DM II), which have potential important financial implications. The present study was designed to expand this examination and to include Type I DM (DMI) patients and random blood glucose (RBG) values. Data were obtained from 234 DM II and 104 DM I patients, over 3 years. Correlation of HbA1 with FPG levels in DM II yielded an r value of 0.61. Correlation of HbA1 with RBG and 2 h post prandial glucose measurements yielded r values of 0.59 and 0.51 respectively, p < 0.001. In DM I, similar correlations gave r values ranging between 0.27 and 0.38, p < 0.01-0.001. Thus while significant correlations exist between HbA1 and FPG and RBG measurements in both DM I and DM II, clinically applicable information on long-term diabetic control can only be achieved from glucose measurements in DM II but the correlation is not sufficiently tight to recommend substitution of plasma glucose for HbA1 determinations, despite the cost advantages.

Audit of bronchial artery embolisation in a specialist respiratory centre.

OBJECTIVE: To audit the use of bronchial arteriography and embolisation for controlling haemoptysis. DESIGN: Retrospective review of radiological and clinical data. SETTING: Brompton and National Heart Hospitals. PATIENTS: 35 patients with severe pulmonary disease in whom 58 bronchial arteriograms were obtained between 1 January 1984 and 31 December 1989 with the intention of bronchial artery embolisation for controlling haemoptysis. MAIN MEASURES: Rate of technical success and cessation of haemoptysis; detailed evaluation of patients, particularly those with major haemoptysis (> 100 ml expectorated blood); and retrospective assessment of the appropriateness of the procedure in each. RESULTS: 58 procedures were performed, nine of which were unsuitable for detailed analysis. Nine procedures were for minor haemoptysis, which subsequently recurred, and 40 for recent major haemoptysis in 26 patients with cystic fibrosis (16) aspergilloma (six), bronchiectasis (three), and an unknown diagnosis (one). The median total volume of haemoptysis in the episode before the procedure was 680 ml (range 270-2200 ml). Embolisation was technically successful in 33/40 procedures, in 17 of which, however, major haemoptysis recurred within 10 days of the procedure, leaving 16 clinically and technically successful procedures in 15 patients. Five patients (three with aspergilloma, two with cystic fibrosis) died of haemoptysis despite attempted embolisation. CONCLUSION: Success rate of bronchial artery embolisation was 40%(16/40). IMPLICATIONS: Bronchial artery embolisation is probably not justified for minor haemoptysis or when performed more than one week after a major haemoptysis. Repeat arteriograms during a single period of haemoptysis are seldom useful. With these criteria 43% fewer procedures would have been performed with no loss of clinical benefit.

Strategies for obtaining compliance with medications regimens.

Case examples of doctor-patient interactions are used to examine educational strategies employed by physicians to obtain compliance with medication regimens from elderly patients. The problems addressed by the physicians included the complexities of pharmaco-therapy in the elderly (the patients each presented multiple problems involving the use of multiple medications), the limited understandings of the drugs showed by patients and their relatives; and the issue of compliance with instructions. Educational strategies that were effective are described.