Parenchymal involvement on CT pulmonary angiography in SARS-CoV-2 Alpha variant infection and correlation of COVID-19 CT severity score with clinical disease severity and short-term prognosis in a UK cohort.

AIM: To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes. MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20-5/1/21. RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001). CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.

Chest CT screening for COVID-19 in elective and emergency surgical patients: experience from a UK tertiary centre.

AIM: To determine the incidence of possible COVID-19-related lung changes on preoperative screening computed tomography (CT) for COVID-19 and how their findings influenced decision-making. To also to determine whether the patients were managed as COVID-19 patients after their imaging findings, and the proportion who had SARS-CoV2 reverse transcriptionpolymerase chain reaction (RT-PCR) testing. MATERIALS AND METHODS: A retrospective study was undertaken of consecutive patients having imaging prior to urgent elective surgery (n=156) or acute abdominal imaging (n=283). Lung findings were categorised according to the British Society of Thoracic Imaging (BSTI) guidelines. RT-PCR testing, management, and outcomes were determined from the electronic patient records. RESULTS: 3% (13/439) of CT examinations demonstrated findings of classic/probable COVID-19 pneumonia, whilst 4% (19/439) had findings indeterminate for COVID-19. Of the total cohort, 1.6% (7/439) subsequently had confirmed RT-PCR-positive COVID-19. Importantly, all the patients with a normal chest or alternative diagnoses on CT who had PCR testing within the next 7 days, had a negative RT-PCR (92/407). There was a change in surgical outcome in 6% (10/156) of the elective surgical cohort with no change to surgical management was demonstrated in the acute abdominal emergency cohort requiring surgery (2/283). CONCLUSION: There was a 7% (32/439) incidence of potential COVID-19-related lung changes in patients having preoperative CT. Although this altered surgical management in the elective surgical cohort, no change to surgical management was demonstrated in the acute abdominal emergency cohort requiring surgery.

Local control, safety, and survival following image-guided percutaneous microwave thermal ablation in primary lung malignancy.

AIM: To determine local control, safety, and survival following percutaneous computed tomography (CT)-guided high-power microwave ablation (MWA) in the treatment of primary lung malignancy at a single institution. MATERIAL AND METHODS: From July 2010 to June 2016, 52 patients (mean age 76.3 years, range 55-91 years) with 61 unresectable primary lung cancers of mean diameter 23.8 mm (range 26-55 mm) underwent MWA in 55 ablation sessions. Tumours were diagnosed at biopsy, or positron-emission tomography (PET) avidity (mean SUV max = 10.51) and interval growth. Statistical analysis was performed by Kaplan-Meier modelling and Cox and logistic regression. RESULTS: Local tumour progression (LTP) was diagnosed in six lesions (10%). Median time to local recurrence was 3 months (range 2-14 months). There was a near 12-fold increased odds of local recurrence if the lesion size was >3 cm (95% confidence interval [CI]: 1.84-75.14; p=0.009). The median inpatient stay was 1 day, with no intra-procedural deaths and a 0% 30-day post-ablation mortality rate. Pneumothorax requiring drain was the most serious complication, occurring in 22% (n=12) of patients. Presence of severe emphysema and predicted forced expiratory volume in 1 second (FEV1) of <50% were found to predict future requirement of a drain (odds ratio [OR] 8.17, 95% CI: 1.62-41.37, p=0.01 and OR: 5.14, 95% CI: 1.28-20.68, p=0.02 respectively), when adjusted for age and gender. Tumour size >3 cm had a hazard ratio of 4.37 compared with tumour size ≤3 cm (95% CI: 1.45-13.17, p=0.009) of risk of cancer death at any time, by Cox regression. CONCLUSION: MWA for primary lung malignancy is a safe and effective treatment for primary lung tumours with outcomes that may be comparable to stereotactic body radiation therapy.

Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey.

BACKGROUND: Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. OBJECTIVES: The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. METHODS: Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. RESULTS: The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg(-1) per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg(-1) vs. 2 mg kg(-1) vs. > 2 mg kg(-1) , the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33-1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04-5·46, P = 0·04, Ptrend < 0·001. CONCLUSIONS: The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.

Altered fibrinolysis in DVT: influence of site of sampling.

Alteration of the fibrinolytic system is considered to be important in the development of deep venous thrombosis (DVT). Using specific assays for tissue plasminogen activator (t-PA) activity, t-PA inhibitor (PAI) and t-PA antigen, we measured these activities in 16 women who developed DVT during their pregnancies. A group of 24 healthy females of comparable age was studied as controls. PAI was increased in 87% of these patients compared to the healthy controls. In some of these patients a defect in release of t-PA from vascular endothelium was found as well. The site at which blood was sampled for analysis appeared to be an important criterion in the ex vivo assessment of functional t-PA reserve and PAI levels, though relatively less so for the latter measurement. The unaffected lower limbs, relative to the unaffected upper limbs, showed an increase in PAI and a demonstrable decrease in t-PA release, both representing increased risk factors for rethrombosis. The affected lower limbs showed similar but more accentuated changes in these parameters.

Differences in coagulation and haemostatic parameters in normal women of childbearing age from different ethnic groups and geographical locations. Task Force on Oral Contraceptives--WHO Special Programme of Research, Development and Research Training in Human Reproduction.

A comparative study of coagulation and fibrinolytic laboratory parameters was undertaken in four countries (Salvador, Brazil; Singapore; Santiago, Chile and Dublin, Ireland) among apparently healthy women of reproductive age. A continuous external quality control scheme of the laboratory measurements was employed to permit comparison among centres. Significant and consistent differences were found between the four centres. In Dublin, the prothrombin time and activated partial thromboplastin time (APTT) were accelerated, and the specific factor assays showed more activity, whereas the antiprotease levels were higher than in the other centres. In Salvador, a contrasting tendency was found with longer prothrombin times and APTT and lower Factor VII and antiprotease levels. The results from the other two centres were approximately midway between these two extremes. The study has revealed important differences in the coagulation and haemostatic tests between women from widely diverse geographical areas. It is not certain whether these are due to ethnic, nutritional or economic factors but they may be related to the apparent varying incidence of thrombosis in these ethnic groups.

A multicentre study of coagulation and haemostatic variables during oral contraception: variations with geographical location and ethnicity. Task Force on Oral Contraceptives--WHO Special Programme of Research, Development and Research Training in Human Reproduction.

A comparative study of the effects of combined oral contraceptives (OC) on coagulation and fibrinolytic variables using standardized laboratory technique and methodology has been performed in Dublin (Ireland), Salvador (Brazil), Santiago (Chile) and Singapore. Of 777 entrants to the study, 622 were randomly allocated to receive one of four different OC formulations. The remainder did not opt for OC. The progestogenic component was levonorgestrel (LNG) in three of the OC formulations and norethisterone acetate (NEA) in the fourth. Results for the three LNG user groups were pooled. The changes in haematological variables observed over 12 months in the LNG and NEA users were examined in relation to the changes seen in the women not on OC. Women in Salvador differed markedly from those in the other three centres, in showing no acceleration of the prothrombin time and no increase in either fibrin plate lysis or plasminogen following the use of OC. After adjusting the findings in OC users for those in non-users, significant differences in response between centres were also detected for activated partial thromboplastin time (accelerated only in Dublin and Santiago), factor VII activity (increased mainly in Salvador and Santiago) and fibrinogen (for which the most marked changes were an increase in Dublin and a decrease in Salvador). This variability between centres in the effects of OC on coagulation and fibrinolysis suggests that OC administration in different populations may not carry equal thrombotic risks.

Maternal-child hepatitis B virus transmission in Singapore.

A study of maternal-infant transmission of hepatitis B virus (HBV) was conducted in Singapore between June 1980 and June 1982. HBsAg carrier rate was highest among Chinese (6.2%) followed by Malay (2.3%) and Indian (0.6%) mothers. The presence of HBeAg in maternal sera correlated well with high titre HBsAg (p = 7.34 X 10(-5)). Overall HBV transmission occurred in 27/56 (48.2%) infants from carrier mothers. The majority of the transmission was perinatal. There was a very strong correlation between transmission and HBeAg status of the mother (p = 1.85 X 10(-9); odds ratio = 68.44) and to a lesser extent with high titre HBsAg (p = 0.002; odds ratio = 6.38). A strong negative correlation was seen between transmission and anti-HBeAg (p = 8.19 X 10(-7); odds ratio = 0.04). At one year 19 (70.4%) infants were still HBsAg positive while seven (25.9%) lost the antigenemia and acquired anti-HBsAg and one developed HBsAg after one year. It could be calculated that perinatal HBV transmission contributed about 18% to the total pool of HBsAg positive infants of one year of age.

Age-related decline in fertility: a link to degenerative oocytes?

OBJECTIVE: To determine whether the age-related decline in fertility is due to degenerative oocytes or to aneuploidy. DESIGN: Retrospective. SETTING: Fertility center of a public and tertiary institution. PATIENT(S): One hundred fifty-one women (ages 24 to 44 years) undergoing 158 cycles of conventional IVF or IVF with intracytoplasmic sperm injection (ICSI) between January 1993 and December 1995 were divided into three age groups (group 1, < or = 34 years; group 2, between 35 and 39 years; and group 3, > or = 40 years). They were selected on the basis of available oocytes that remained unfertilized after IVF and that had analyzable chromosomes. INTERVENTION(S): Standard pituitary down-regulation and ovarian stimulation with FSH and hMG were done for both IVF and ICSI patients. In addition, all patients were given luteal phase support with P, administered orally, via pessaries, or by IM injections from the day of transfer. MAIN OUTCOME MEASURE(S): Fertilization rates and pregnancy rates (PRs), and cytogenetic analyses of unfertilized oocytes. RESULT(S): Although fertilization rates were not different among women in groups 1, 2, and 3 (50.9%, 49.3%, and 37.9%, respectively), PRs were significantly lower between groups 1 and 3 (43.2% versus 14.3%). A total of 383 oocytes were examined, of which 287 (75%) could be karyotyped. Of these, 201 oocytes showed a normal 23,X karyotype (70%), 40 (13.9%) were aneuploid, 24 (8.4%) were diploid, 12 (4.2%) had structural aberrations, and 13 (4.5%) had single chromatids only. No increase in the aneuploidy rate was detected between groups 1 and 2 (14.8% versus 12.4%). However, highly significant differences in the rate of oocyte chromosome degeneration, characterized by chromosomes splitting into unassociated chromatids, were observed with increasing age (group 1, 23.7%; group 2, 52.0%; and group 3, 95.8%). CONCLUSION(S): It seems that the age-related decline in fertility may be due more to degenerative oocytes than to aneuploidy. A decline in the number of oocytes retrieved with age may be of less importance than the decline in oocyte quality. Women in the older age group have a higher chance of achieving pregnancy from ovum-donation programs than by persisting in using their own aged oocytes, which have a very poor prognosis for success.

PIP: The hypothesis that the fertility decline observed in women over 40 years old is linked more to degenerative oocytes than to age-associated aneuploidy was investigated in 151 women 24-44 years old who underwent a total of 158 in vitro fertilization (IVF) cycles at Singapore General Hospital during 1993-95. Fertilization rates were 50.9% in women 34 years or younger, 49.3% in those 35-39 years old, and 37.9% in women 40 years or older. The pregnancy rates were 43.2%, 32.7%, and 14.3%, respectively. 287 (74.9%) of the 383 unfertilized oocytes could be karyotyped fully. The total chromosome abnormality rate was 30.3%; this included aneuploidy (13.9%), diploidy (8.4%), structural aberrations (4.2%), and single chromatids only (4.5%). A relationship between increased maternal age and an increase in the aneuploidy rate could not be assessed because of the small sample size in the oldest age group. The rate of chromatid separation increased significantly from 23.8% in the youngest age group to 95.8% in the oldest age group. This rate did not differ between in vitro fertilization and intracytoplasmic sperm injection. The degeneration evident in the majority of oocytes of older women presumably reflects decades of metabolic arrest at the dictyate stage. These findings suggest that the decline in the number of oocytes retrieved with age may be of less importance than the decline in oocyte quality. Women in the older age group have a greater likelihood of achieving pregnancy from ovum donation programs.

Trace elements in blood and seminal plasma and their relationship to sperm quality.

The concentrations of cadmium, lead, selenium, and zinc in blood and seminal plasma were determined in 221 Singapore men. The relationship of trace element concentration to sperm density, motility, morphology, and semen volume was also investigated. The concentrations of elements were in the following descending order: Zn > Se > Pb > Cd. Except for zinc, the concentrations were generally higher in blood than in seminal plasma. The mean concentration of zinc in seminal plasma (ZnSP) was about 30 times higher than in blood (ZnB). A significant inverse correlation was observed between blood cadmium levels (CdB) and sperm density (r = -0.24, P < 0.05) in oligozoospermic men (sperm density below 20 million/mL) but not in normospermic men. Cadmium in seminal plasma (CdSP) was also associated with low semen volume (r = -0.29, P < 0.05). These findings suggest that cadmium may have an effect on the male reproductive system. In contrast, positive correlations were observed between concentrations of selenium and zinc in seminal plasma (SeSP and ZnSP) and sperm density in normospermic men but not in oligozoospermic men. The correlation coefficients with sperm density for SeSP and ZnSP were 0.35 (P < 0.05) and 0.41 (P < 0.01), respectively. The concentrations of lead in blood (PbB) or seminal plasma (PbSP) did not appear to have any correlation with the sperm parameters studied.

Semen parameters in workers exposed to trichloroethylene.

The objective of this study was to examine the effects of TCE on spermatogenesis among a group of workers with varying degrees of exposure to TCE in an electronics factory. A total of 124 workers participated in the study for which 85 were included in the study based on the selection criteria. Semen analysis included volume, sperm density, sperm viability, motility, and morphology. Each worker also had urine collected and analyzed for trichloroacetic acid (TCA) on the day (end of work week) the semen was given. Personal monitoring for environmental TCE exposure was conducted for 12 workers. The mean environmental TCE level was 29.6 ppm (range 9 to 131) and the mean urine TCA was 22.4 mg/g creatinine (range 0.8 to 136.4). The majority of the workers had normal sperm volume (71.8%), density (88.2%), and motility (64.7%). However, the subjects had a low percentage of normal sperm morphology. There were no significant differences in the mean sperm parameters among the "high exposure" (urine TCA > or = 25 mg/g creatinine) and "low exposure" (urine TCA < 25 mg/g creatinine) groups except for sperm density. Prevalence rate ratios of hyperzoospermia were higher with increasing urine TCA levels compared to the "low exposure" group (even after adjusting for marital status of the subjects), suggesting a dose-response relationship.

Experience of a comprehensive infertility clinic in the Department of Obstetrics and Gynaecology, University of Singapore.

PIP: The diagnosis, treatment, and pregnancy outcome for 709 infertile couples who attended the comprehensive infertility clinic of the University of Singapore's Department of Obstetrics and Gynecology from 1970-1974 are presented. Investigations for most of the couples were completed within 3 months. This short investigative period was attributable primarly to the use of laparoscopy to diagnose female infertility. In 22.5% of the 709 cases infertility was due to ovulation problems. After treatment eith either clomiphene, human pituitory gonadotrophin, or a combination of clomiphene and human chorinic gonadotrophin, pregnancy was achieved in 30.6% of the cases. 11.7% or 83 of the 709 infertility cases were attributed to blocked tubes. 28 of these patients received tubal surgery, but only 14.3% or 4 of these cases resulted in pregnancy. In 14.7% of the 709 cases, infertility was attributed to endometriosis. 90% of the patients with endometriosis were asymptomatic, and the liesons discovered by laparoscopy, were very small. Pregnancy eventually occurred in 27.6% of the cases treated for endometriosis. In 5.8% of the 709 cases infertility was due to mixed gynecological problems, and after treatment, conception occurred among 31.7% of the cases. For 23.1%, or 147 of the 709 couples, infertility was attributed to either oligospermia or azoospermia. 85 of the 147 patients were given hormone therapy and in 12.9% of these cases pregnancy was achieved. 14 of the 147 patients were treated with antibotics for 3-6 months and in 14.3% of these cases pregnancy was achieved. 9 of the 147 patients were surgically treated and in 4 of these cases pregnancy later occurred. 20 of the 147 couples were treated with artifical insemination of donor semen and in 25.0% of these cases pregnancy occurred. Another 19 of the 147 cases were treated with artificial insemination with the husband's semen and conception occurred in 26.8% of these cases. The remaining 22.1% of the 709 couples were apparently normal and 47.8% of these untreated couples later achieved pregnancy.^ieng

The role of fine needle aspiration for breast cancer in the climacteric--a preliminary report.

Fine needle biopsy has been used with great accuracy in the diagnosis of breast tumours. There have been few reports on its efficacy as an adjunct to other breast screening techniques like x-ray mammography. Abnormal mammograms in the absence of a palpable breast lump are sometimes detected in the climacteric and these pose a problem of tissue sampling for pathologic diagnosis. We have tried to evaluate the technique of radiologically guided fine needle aspiration in such patients. Our report is of an initial series of 13 cases of non-palpable, mammographically abnormal breast lesions. Eight cases were fibroadenoma, 4 cases mammary dysplasia and 1 a benign breast lesion. Representative cytologic samples were obtained in 11 of our 13 cases. Cytologic diagnosis should be correlated with mammographic findings.

Chromosomes of oocytes failing in-vitro fertilization.

Of 263 oocytes that failed to fertilize after in-vitro fertilization and were sent for cytogenetic investigation, 179 (68.1%) were analysable. More than 72.0% were normal metaphase II haploids (23,X). Hyperhaploidy, hypohaploidy and complex cases made up a total aneuploidy rate of 12.3%, while 10.1% were diploid. In addition, there were five oocytes with structural aberrations and eight yielded chromatids only. The total chromosome aberration rate was 29.1%. No significant difference was found between the aneuploidy rate and maternal age. Here we present photographic evidence of oocytes with extra whole chromosomes and extra single chromatids. We suggest that both predivision and nondisjunction contribute to the formation of trisomy in man.

Concentrations of heavy metals in maternal and umbilical cord blood.

Concentrations of lead, cadmium, methylmercury and total mercury were measured in maternal and umbilical cord blood using graphite atomic absorption spectrometry. Two essential metals, copper and zinc, were also determined using ion chromatography. Lead, copper and zinc were found to be lower in the cord blood whereas methylmercury and total mercury were higher in cord blood than in maternal blood. Little differences were noted for cadmium in maternal and cord blood. Significant positive correlations were observed between the concentrations in maternal and cord blood with regard to lead (correlation coefficient, r = 0.44), copper (r = 0.34), zinc (r = 0.29), methylmercury (r = 0.44) and total mercury (r = 0.58). These results suggest that, like essential metals, most heavy metals can move rather freely across the human placenta. The potential health effects of heavy metal transfer from mothers to young infants cannot be discounted.