Hormone replacement therapy in prevention of morbidity and mortality in the older woman: part III: potential adverse effects of hormone replacement therapy

OBJECTIVES: The objective of this four part series is to review for the practicing clinician the extensive and sometimes contradictory literature on the effects of estrogen replacement therapy (ERT) and hormone replacement therapy (HRT) in the postmenopausal woman. This third article reviews HRT and the potential excess morbidity from breast cancer, endometrial cancer, venous thromboembolism (VTE), and coronary heart disease (CHD). DESIGN: Studies reviewed were obtained through Medline searches, examination of citations in the articles reviewed from those searches,interviews with local experts in geriatrics, cardiology, and women's health. CONCLUSIONS: Long-term HRT seems to be associated with a small increased risk for breast cancer. The risk of endometrial cancer in women with a uterus using ERT can be eliminated completely with the use of combination estrogen and progestin. HRT may be associated with a small increased risk for VTE; however, the absolute morbidity and mortality attributable to VTE is small and unlikely to impact the net benefit of HRT significantly. Although there is considerable data favoring a beneficial effect of HRT on CHD, initiation of HRT in women with established CHD may be associated with increased risk of adverse cardiac events in the first year after initiation. In counseling patients about the use of long-term HRT, the balance of these risks and the effect of co-morbid illness in the geriatric population should be addressed. Discussion of HRT and the aging brain (stroke, dementia), the net benefit of long-term HRT, and decision-making for the individual patient is forthcoming in the final article of this four-part series.     

"Drug mules" as a radiological challenge: sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

Purpose

The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox^®) in the detection of internal cocaine containers.

Methods

Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16–45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT = 35, nDR = 70, nLSDR = 30. An overall calculation of all “drug mules” and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet.

Results

There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific.

Conclusions

CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage.     

Diffuse endometritis in the setting of umbilical endometriosis: a case report

BACKGROUND: Umbilical endometriosis is rare and can be a challenging diagnosis in the absence of classic signs and symptoms. CASE: A case of severe, primary, spontaneous umbilical endometriosis with foci of plasma cell endometritis and diffuse stromal lymphovascular presence occurred. CONCLUSION: Despite a lengthy differential, endometriosis must be considered in the evaluation of an umbilical mass. The presence of plasma cell endometritis and stromal lymphovascular elements in the absence of pelvic endometriosis lends evidence to the theory of lymphovascular transport as an etiology of extrapelvic endometriosis.     

Native and activated antithrombin inhibits TMPRSS2 activity and SARS-CoV-2 infection

Host cell proteases such as TMPRSS2 are critical determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tropism and pathogenesis. Here, we show that antithrombin (AT), an endogenous serine protease inhibitor regulating coagulation, is a broad-spectrum inhibitor of coronavirus infection. Molecular docking and enzyme activity assays demonstrate that AT binds and inhibits TMPRSS2, a serine protease that primes the Spike proteins of coronaviruses for subsequent fusion. Consequently, AT blocks entry driven by the Spikes of SARS-CoV, MERS-CoV, hCoV-229E, SARS-CoV-2 and its variants of concern including Omicron, and suppresses lung cell infection with genuine SARS-CoV-2. Thus, AT is an endogenous inhibitor of SARS-CoV-2 that may be involved in COVID-19 pathogenesis. We further demonstrate that activation of AT by anticoagulants, such as heparin or fondaparinux, increases the anti-TMPRSS2 and anti-SARS-CoV-2 activity of AT, suggesting that repurposing of native and activated AT for COVID-19 treatment should be explored.     

CD40 ligand and interferon‐γ induce an antimicrobial response against Mycobacterium tuberculosis in human monocytes

The ability of T cells to activate antimicrobial pathways in infected macrophages is essential to host defence against many intracellular pathogens. Here, we compared the ability of two T‐cell‐mediated mechanisms to trigger antimicrobial responses against Mycobacterium tuberculosis in humans, CD40 activation and the release of interferon‐γ (IFN‐γ). Given that IFN‐γ activates a vitamin D‐dependent antimicrobial response, we focused on induction of the key components of this pathway. We show that activation of human monocytes via CD40 ligand (CD40L) and IFN‐γ, alone, and in combination, induces the CYP27b1‐hydroxylase, responsible for the conversion of 25‐hydroxyvitamin D (25D) to the bioactive 1,25‐dihydroxyvitamin D (1,25D), and the vitamin D receptor (VDR). The activation of the vitamin D pathway by CD40L and IFN‐γ results in up‐regulated expression of the antimicrobial peptides, cathelicidin and DEFB4, as well as induction of autophagy. Finally, activation of monocytes via CD40L and IFN‐γ results in an antimicrobial activity against intracellular M. tuberculosis. Our data suggest that at least two parallel T‐cell‐mediated mechanisms, CD40L and IFN‐γ, activate the vitamin D‐dependent antimicrobial pathway and trigger antimicrobial activity against intracellular M. tuberculosis, thereby contributing to human host defence against intracellular infection.     

Rotational instability of the knee: internal tibial rotation under a simulated pivot shift test

Introduction  Recently, several publications investigated the rotational instability of the human knee joint under pivot shift examinations and reported the internal tibial rotation as measurement for instrumented knee laxity measurements. We hypothesize that ACL deficiency leads to increased internal tibial rotation under a simulated pivot shift test. Furthermore, it was hypothesized that anatomic single bundle ACL reconstruction significantly reduces the internal tibial rotation under a simulated pivot shift test when compared to the ACL-deficient knee. Methods  In seven human cadaveric knees, the kinematics of the intact knee, ACL-deficient knee, and anatomic single bundle ACL reconstructed knee were determined in response to a 134 N anterior tibial load and a combined rotatory load of 10 N m valgus and 4 N m internal tibial rotation using a robotic/UFS testing system. Statistical analyses were performed using a two-way ANOVA test. Results  Single bundle ACL reconstruction reduced the anterior tibial translation under a simulated KT-1000 test significantly compared to the ACL-deficient knee (P < 0.05). After reconstruction, there was a statistical significant difference to the intact knee at 30° of knee flexion. Under a simulated pivot shift test, anatomic single bundle ACL reconstruction could restore the intact knee kinematics. Internal tibial rotation under a simulated pivot shift showed no significant difference in the ACL-intact, ACL-deficient and ACL-reconstructed knee. Conclusion  In conclusion, ACL deficiency does not increase the internal tibial rotation under a simulated pivot shift test. For objective measurements of the rotational instability of the knee using instrumented knee laxity devices under pivot shift mechanisms, the anterior tibial translation should be rather evaluated than the internal tibial rotation. This study was supported in part by a grant of the German Speaking Association of Arthroscopy (AGA).     

Serum mannan-binding lectin-associated serine protease 2 levels in colorectal cancer: relation to recurrence and mortality.

PURPOSE: Mannan-binding lectin-associated serine protease 2 (MASP-2) is a plasma protein involved in inflammatory processes. MASP-2 circulates in complex with the protein mannan-binding lectin (MBL) or ficolins, and is activated to recruit the complement system when MBL binds to its targets. The level of MASP-2 is genetically determined, and the aim of the present study was to evaluate the effect of MASP-2 levels on postoperative infection, recurrence and survival. EXPERIMENTAL DESIGN: MASP-2 concentrations were determined in serum from 605 patients collected before elective resection for primary colorectal cancer. The primary end points were postoperative infection, time to any recurrence, and time to death. The median time of follow-up was 7.9 years. RESULTS: MASP-2 levels were not correlated to postoperative infections (P = 0.49). High MASP-2 levels significantly correlated with recurrent cancer disease [P = 0.03; hazard ratio (HR) = 1.4; 95% confidence interval (CI), 1.0-2.0] and with poor survival (P = 0.0005; HR = 1.4; 95% CI, 1.2-1.7). Multivariate statistical analysis, including age, gender, Dukes' stage of disease, tumor localization, and postoperative pneumonia, showed that the MASP-2 level had an independent prognostic value in the patients (P = 0.0001; HR = 1.5; 95% CI, 1.2-1.8). CONCLUSION: In the cohort of patients with colorectal cancer investigated, MASP-2 concentration in serum proved to be an independent prognostic marker with high MASP-2 levels predicting recurrence and poor survival. Postoperative infection could not be shown to be associated with MASP-2 levels.     

Effectiveness of various forms of therapy in chronic cardiovascular diseases--a vector analysis of the transition probabilities of degrees of severity

The present findings result from a check of probationers representative for approx. 280,000 inhabitants of defined territories, who had been designated as suspects of heart and vessel disease on grounds of X-ray-morphological criterions (classification by Richter). Those about 3,000 suspects, subdivided into 3 comparable patient groups A, B and C, underwent different regimes of treatment of outpatient medical practice after standardized and noninvasive diagnostics in a follow-up during 5 years and had been valued by means of a problem-specific grading. The comparative analysis about the distribution of severe degrees concerning hypertension and coronary heart disease after the conclusion of the intervention showed significant differences concerning the results of treatment to the credit of the patient group A (treated by specialists) contrary to the patient group B (treated by family doctors) and patient group C (principle of announcing the patients themselves). Also the patient group B showed significantly better results of therapy compared with the patient group C. In addition to the concluding rating the estimation of yearly transition of severe degrees gave an insight into the therapeutical decision of the person who looks after as well as the different distribution of severe degrees of special heart diseases in dependence on the starting severe degree in the special period of intervention conditioned on the therapy. The results gain exceptional importance for practice on the grounds of methodics of the study-automatable classification of dv-thorax-X-ray pictures, problem-specific grading of noninvasive, simple parameters, variants of therapy in dependence on the graduated system of medical care.     

Influence on clinical parameters of depressomassage (part I): The effects of depressomassage on color and transepidermal water loss rate in burn scars: A pilot comparative controlled study

Objective

Depressomassage is a non-invasive massage technique using a mechanical suction device that is used in the treatment of traumatic or burn scars. Since color and transepidermal water loss (TEWL) are respectively the most important physical and physiological characteristic of hypertrophic scar formation, we wanted to investigate the effects of depressomassage on the recovery of color and TEWL in burn scars compared to the traditional physiotherapy.