SARS-CoV-2 and pregnancy outcomes under universal and non-universal testing in Sweden: register-based nationwide cohort study.

OBJECTIVE: To assess associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pregnancy outcomes considering testing policy and test-positivity-to-delivery interval. DESIGN: Nationwide cohort study. SETTING: Sweden. POPULATION: From the Pregnancy-Register we identified 88 593 singleton births, 11 March 2020-31 January 2021, linked to data on SARS-CoV-2-positivity from the Public Health Agency, and information on neonatal care admission from the Neonatal Quality Register. Adjusted odds ratios (aORs) were estimated stratified by testing-policy and test-positivity-to-delivery interval. MAIN OUTCOME MEASURES: Five-minute Apgar score, neonatal care admission, stillbirth and preterm birth. RESULTS: During pregnancy, SARS-CoV-2 test-positivity was 5.4% (794/14 665) under universal testing and 1.9% (1402/73 928) under non-universal testing. There were generally lower risks associated with SARS-CoV-2 under universal than non-universal testing. In women testing positive >10 days from delivery, generally no significant differences in risk were observed under either testing policy. Neonatal care admission was more common (15.3% versus 8.0%; aOR 2.24, 95% CI 1.62-3.11) in women testing positive ≤10 days before delivery under universal testing. There was no significant association with 5-minute Apgar score below 7 (1.0% versus 1.7%; aOR 0.64, 95% CI 0.24-1.72) or stillbirth (0.3% versus 0.4%; aOR 0.72, 95% CI 0.10-5.20). Compared with term births (2.1%), test-positivity was higher in medically indicated preterm birth (5.7%; aOR 2.70, 95% CI 1.60-4.58) but not significantly increased in spontaneous preterm birth (2.3%; aOR 1.12, 95% CI 0.62-2.02). CONCLUSIONS: Testing policy and timing of test-positivity impact associations between SARS-CoV-2-positivity and pregnancy outcomes. Under non-universal testing, women with complications near delivery are more likely to be tested than women without complications, thereby inflating any association with adverse pregnancy outcomes compared with findings under universal testing. TWEETABLE ABSTRACT: Testing policy and time from SARS-CoV-2 infection to delivery influence the association with pregnancy outcomes.

Direct oral anticoagulant use and risk of severe COVID-19.

BACKGROUND: Hypercoagulability and thromboembolism are prominent features of severe COVID-19, and ongoing anticoagulant use might be protective. METHODS: We conducted a nationwide register-based cohort study in Sweden, February through May, 2020, to assess whether ongoing direct oral anticoagulant (DOAC) use was associated with reduced risk of hospital admission for laboratory-confirmed COVID-19, or a composite of intensive care unit (ICU) admission or death due to laboratory-confirmed COVID-19. RESULTS: DOAC use (n = 103 703) was not associated with reduced risk of hospital admission for COVID-19 (adjusted hazard ratio [aHR] [95% confidence interval] 1.00 [0.75-1.33] vs. nonuse atrial fibrillation comparator [n = 36 875]; and aHR 0.94 [0.80-1.10] vs. nonuse cardiovascular disease comparator [n = 355 699]), or ICU admission or death due to COVID-19 (aHRs 0.76 [0.51-1.12], and 0.90 [0.71-1.15], respectively). CONCLUSION: Ongoing DOAC use was not associated with reduced risk of severe COVID-19, indicating that prognosis would not be modified by early outpatient DOAC initiation.

Human papillomavirus vaccination of adult women and risk of autoimmune and neurological diseases.

BACKGROUND: Since 2006, human papillomavirus (HPV) vaccines have been introduced in many countries worldwide. Whilst safety studies have been reassuring, focus has been on the primary target group, the young adolescent girls. However, it is also important to evaluate safety in adult women where background disease rates and safety issues could differ significantly. OBJECTIVE: We took advantage of the unique Danish and Swedish nationwide healthcare registers to conduct a cohort study comparing incidence rate ratios (RRs) of 45 preselected serious chronic diseases in quadrivalent HPV (qHPV)-vaccinated and qHPV-unvaccinated adult women 18-44 years of age. METHODS: We used Poisson regression to estimate RRs according to qHPV vaccination status with two-sided 95% confidence intervals (95% CIs). RESULTS: The study cohort comprised 3 126 790 women (1 195 865 [38%] Danish and 1 930 925 [62%] Swedish) followed for 16 386 459 person-years. Vaccine uptake of at least one dose of qHPV vaccine was 8% in the cohort: 18% amongst Danish women and 2% amongst Swedish. We identified seven adverse events with statistically significant increased risks following vaccination-Hashimoto's thyroiditis, coeliac disease, localized lupus erythematosus, pemphigus vulgaris, Addison's disease, Raynaud's disease and other encephalitis, myelitis or encephalomyelitis. After taking multiple testing into account and conducting self-controlled case series analyses, coeliac disease (RR 1.56 [95% confidence interval 1.29-1.89]) was the only remaining association. CONCLUSION: Unmasking of conditions at vaccination visits is a plausible explanation for the increased risk associated with qHPV in this study because coeliac disease is underdiagnosed in Scandinavian populations. In conclusion, our study of serious adverse event rates in qHPV-vaccinated and qHPV-unvaccinated adult women 18-44 years of age did not raise any safety issues of concern.

Multiple sclerosis and risk of Parkinson's disease: a Danish nationwide cohort study.

BACKGROUND AND PURPOSE: Case reports have observed a co-occurrence of multiple sclerosis (MS) and Parkinson's disease (PD) and it has been hypothesized that MS lesions could affect dopaminergic pathways causing parkinsonism. Our aim was to examine the association between MS and PD in a historically prospective cohort study using Danish nationwide register data. METHODS: Multiple sclerosis patients identified in the Multiple Sclerosis Registry were followed for PD from 1977 to 2011 in the National Patient Register. As measures of relative risk, ratios of observed to expected incidence rates of first hospitalization for PD amongst persons with MS were used, i.e. standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). RESULTS: Amongst 15,557 MS patients 26 cases of PD were observed versus 26.51 expected, reflecting no overall increased risk of PD (SIR 0.98, 95% CI 0.67-1.44). Similar estimates were seen for female (SIR 0.99, 95% CI 0.58-1.67) and male MS patients (SIR 0.97, 95% CI 0.55-1.72). Likewise, no increased risk of PD amongst MS patients was observed in a robustness analysis backdating the date of diagnosis of PD by 5 years to account for the time lag between disease onset and first hospital contact with PD (SIR 0.57, 95% CI 0.32-1.00). CONCLUSION: Our data do not suggest an increased risk of PD amongst patients with MS.

Elevated intraperitoneal matrix metalloproteinases-8 and -9 in patients who develop anastomotic leakage after rectal cancer surgery: a pilot study.

OBJECTIVE: Experimental studies suggest that matrix metalloproteinase (MMP) enzymes mediate the early tissue breakdown that leads to a decrease in intestinal anastomotic strength. Patients with upregulation of MMPs in intestinal biopsies have an increased rate of anastomotic leakage. We measured MMPs and their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] in postoperative intraperitoneal fluid after rectal cancer surgery, and hypothesized that they would be elevated in patients who later would develop anastomotic leakage. METHOD: Twenty-nine patients with rectal carcinoma underwent low anterior resection of the rectum for cancer. Intraperitoneal fluid was collected via a pelvic drain at a median of 4 h postoperatively. MMP-1, -2, -3, -7, -8, -9 and -13 were determined using particle-based multiplex flow-cytometry. TIMP-1 and -2 were measured by enzyme-linked immunosorbent assays. MMP-9 was considered the main outcome variable. RESULTS; Ten patients developed anastomotic leakage. These patients had increased intraperitoneal MMP-9 [median difference (m.d.) 29%; P = 0.03] and MMP-8 (m.d. 58%; P = 0.02), compared with patients who did not develop leakage. There were no differences between the groups for other MMPs and TIMPs. CONCLUSION: Matrix metalloproteinase-8 and -9 appear to have an important role in the development of anastomotic leakage and may be promising pharmacological targets to protect anastomotic integrity. We suggest further investigation of MMPs as markers for anastomotic leakage.

Elevation of systemic matrix metalloproteinases 2 and 7 and tissue inhibitor of metalloproteinase 2 in patients with a history of Achilles tendon rupture: pilot study.

OBJECTIVES: In this study, serum levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) between patients with a history of Achilles tendon rupture and blood donor controls were compared, and their relation to mechanical properties of the tendons during healing were studied. METHODS: More than 3 years after injury, serum levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9 and MMP-13, TIMP-1 and TIMP-2 in eight patients who had Achilles tendon rupture were measured. Twelve blood donors served as controls. During the early phase of healing, the tendon modulus of elasticity was calculated from radiostereometric data and tendon cross-sectional area. RESULTS: Patients with a history of Achilles tendon rupture had increased levels of MMP-2 (median difference 10%, p=0.01), MMP-7 (median difference 15%, p=0.02) and TIMP-2 (median difference 36%, p=0.02), compared with controls. Levels of MMP-7, measured 3 years after injury, correlated inversely to tendon modulus of elasticity (r(s)=20.83, p=0.02) and positively to tendon elongation (r(s)=0.74, p=0.05) during the early phase of healing. There was a trend towards positive correlation between MMP-7 and cross-sectional area during the early phase of healing (r(s)=0.67, p=0.08). CONCLUSIONS: Patients with a history of Achilles tendon rupture appear to have elevated levels of MMP-2, MMP-7 and TIMP-2 in serum. In these pilot data, the view that the MMP-TIMP system is involved in tendinopathy is supported and that disturbances in proteolytic control might be generalised are suggested.

Regulation of intestinal barrier function by signal transducer and activator of transcription 5b.

BACKGROUND: Colon epithelial cell (CEC) apoptosis and nuclear factor-kappaB (NF-kappaB) activation may compromise barrier function, and it has been reported that signal transducer and activator of transcription 5b (STAT5b)-deficient mice exhibit increased susceptibility to colitis. It is hypothesised that the growth hormone (GH) target STAT5b maintains mucosal barrier integrity by promoting CEC survival and inhibiting NF-kappaB activation. METHODS: The GH effect upon mucosal injury due to 2,4,6-trinitro-benzenesulfonic acid (TNBS) administration was determined in STAT5b-deficient mice and wild-type (WT) controls. The effect of STAT5b deficiency upon CEC survival and NF-kappaB activation was determined and related to differences in intestinal permeability and bacterial translocation. RNA interference (RNAi) was used to knock down STAT5b expression in the T84 CEC line, and the effect upon basal and GH-dependent regulation of proapoptotic and inflammatory pathways induced by tumour necrosis factor alpha (TNFalpha) was determined. RESULTS: GH suppression of mucosal inflammation in TNBS colitis was abrogated in STAT5b-deficient mice. STAT5b deficiency led to activation of a proapoptotic pattern of gene expression in the colon, and increased mucosal permeability. The frequency of apoptotic CECs was increased in STAT5b-deficient mice while tight junction protein abundance was reduced. This was associated with upregulation of CEC Toll-like receptor 2 expression and NF-kappaB activation. STAT5b knockdown in T84 CEC increased TNFalpha-dependent NF-kappaB and caspase-3 activation. GH inhibition of TNFalpha signalling was prevented by STAT5b knockdown. CONCLUSION: STAT5b maintains colonic barrier integrity by modulating CEC survival and NF-kappaB activation. STAT5b activation may therefore represent a novel therapeutic target in inflammatory bowel disease.

Autogenous transplantation of teeth with complete root formation: two case reports.

AIM: Autotransplantation is an alternative treatment for replacing lost teeth when suitable donor teeth are available. This paper presents two cases of successful autogenous tooth transplantation. SUMMARY: Two third molars with complete root development were autogenously transplanted from their original sockets into new recipient sites on the same side of the mouth, one in the maxilla and one in the mandible. In both cases, the third molars were transplanted immediately after the first molar extractions. To provide better adaptation of the donor teeth, the recipient alveolar sites were remodelled using surgical burs. Semi-rigid splints were maintained for 45 and 15 days, respectively. Root canal treatment commenced one a week after transplantation and the canals were medicated with a calcium hydroxide paste before they were filled. Clinical and radiographic findings after 5 and 3 years of follow-up, respectively, are discussed in relation to the literature. KEY LEARNING POINTS: Autogenous transplantation of teeth with complete root formation may be considered as a viable treatment option to conventional prosthetic and implant rehabilitation for both therapeutic and economic reasons. Careful surgical and endodontic procedure, together with careful case selection may lead to satisfactory aesthetic and functional outcomes.

Does visceral ischemia play a role in the pathogenesis of acute acalculous cholecystitis?

Acute acalculous cholecystitis is a virulent disease of uncertain etiology observed most commonly in critically ill patients. Although the precise mechanism is unknown, the most commonly postulated theories regarding its pathogenesis are bile stasis, sepsis, and ischemia. The role of ischemia in this process, whose etiology is multifactorial, has been difficult to elucidate. Consequently, we report two patients who developed acute acalculous cholecystitis without apparent risk for the disease other than severe visceral atherosclerosis. Both patients had symptomatic mesenteric vascular disease requiring revascularization and developed fulminant acalculous cholecystitis temporally related to exacerbation of their visceral ischemia. These cases suggest that patients with visceral atherosclerosis may be at increased risk for acute acalculous cholecystitis, perhaps due to impaired mucosal resistance when other factors, such as bile statis and sepsis, are also present.

Breastfeeding decline in urban China: an exploratory study.

"Retrospective data collected in two urban neighborhoods of Tianjin, People's Republic of China, reveal a decline in the rate and duration of breastfeeding since the mid-1930's.... The evidence indicates that breastfeeding declined as women became involved in work outside the home, as they adopted a form of postmarital residence that separated them from other relatives, as income increased, and as their rural origins decreased. No evidence was found to indicate a relationship between breastfeeding and parity or sex preferences."

Thoracic outlet syndrome. Electrophysiologic reappraisal.

Eighteen patients with thoracic outlet syndrome (TOS) were examined with somatosensory evoked potentials (SEPs). All the patients had normal median N9 (brachial plexus) amplitudes, whereas 12 had low-amplitude ulnar N9 potentials. The conduction in the ulnar nerve from N9 to N13 (brachial plexus to cord) was prolonged in seven of 18 patients. The combination of the ulnar N9 amplitude, the ulnar N9 to N13 conduction, and routine ulnar F-wave determination yielded positive quantitative diagnostic information in 17 of 18 cases. The SEPs appear to be a reliable, sensitive, quantitative, and non-invasive diagnostic tool in examining patients with TOS.

Traumatic arterial spasm--rarity or nonentity.

Despite numerous opinions in literature questioning the existence of traumatic arterial spasm we believe that, although infrequent, the condition nevertheless occurs. A survey of the vascular literature on this subject appears to support this view. Spasm, when found, should be treated by resection of the arterial segment and its replacement with an appropriate graft unless spasm is relieved by vasodilation.

Prevention of compression thrombosis by modification of axillofemoral graft.

Modified placement of the long limb of an axillobifemoral graft will prevent compression thrombosis and may enhance long-term patency of these grafts.

Current status of surgery of the omentum.

The greater omentum is a unique organ with multipotential properties. A simple procedure converts it into a vascularized pedicle that may be utilized throughout the body. Knowledge of the possible applications of free or pedicled omental grafts will significantly add to the armamentarium of a clinical and experimental surgeon.

Fungal infection of a vascular prosthesis.

Chronic debilitating hematological disorders and cytotoxic drugs may create conditions causing a predisposition to fungal infections of vascular grafts. Under such circumstances routine bacteriological investigations should be supplemented by specific fungal media cultures and microscopic examination of removed infected graft.

Progressive occlusive thrombarteriopathy: a case report.

A case of occlusive arterial disease of obscure nature and etiology is reported. The most puzzling aspect of this case was an apparent lack of correlation between the acute, progressive clinical course of the disease, especially in its final stages and the absence of any corresponding acute changes on microscopic examination of the affected vessels. Furthermore the combination of clinical features and pathologic findings--particularly the thrombotic involvement of the heart and the thoracic aorta by a process starting in the small and medium size vessels of the lower extremities--is not consistent with any of the recognized syndromes leading to a thrombotic occlusion of the arterial system. We conclude that the case represents an obscure syndrome of progressive occlusive thrombarteriopathy, perhaps related to a cumulative effect of heavy smoking, alcoholism, and drug addiction. It is possible that increased coagulability of the blood contributed to the thrombotic process but was not recognized by means of the hematologic studies performed.

Arteriovenous fistula and forward hypertension in the portal circulation.

The notorious predilection for rupture of splenic artery aneurysms in women of childbearing age is once more stressed by this case report. Although such ruptures usually result in a catastrophic interabdominal bleeding, in rare instances they lead to the formation of an arteriovenous fistula and consequent portal hypertension. Arterialization of the portal vein results in a progressive development of intrinsic hepatic morphologic changes and hepatoportal sclerosis, which further elevate the pressure in the portal system. This combination of pathophysiologic hemodynamic features closely resembles the original concept of Banti. He postulated that portal hypertension began with pathologic changes within the spleen which were associated with an increased blood flow through this organ. This led to increased flow and pressure in the portal venous system and ultimately cumulated in cirrhosis of the liver. This concept of the pathophysiology of portal hypertension has been universally abandoned, but it could serve as a model of the sequelae of an arteriovenous communication within the portal system.