Occult Loss Research Articles

The Role of Endoscopy in Investigating the Causes of Persistent Anaemia in Post-operative Fractured Neck of Femur Patients.

Introduction Post-operative anaemia in hip fracture patients has been associated with increased risk of blood transfusion, poorer functional outcomes, increased morbidity and mortality. Patients with persisting drop in haemoglobin after fractured neck of femur with no obvious source of blood loss are often referred for endoscopy to find the cause of anaemia. The reported incidence of perioperative acute upper gastrointestinal bleeding varies from 1 to 15%. Objective The aim of our study is to find out the usefulness of endoscopy in finding gastrointestinal causes leading to the occult loss of blood causing irreversible anaemia in post-operative neck of femur fractures. Material and methods The orthogeriatric unit conducted a study using retrospective dataon neck of femur fracture patients from January 2015 to December 2020. Out of 1863 cases, 918 (49.3%) developed post-operative anaemia. Forty-five patients (5%) with refractory anaemia underwent endoscopy referral. Patient demographics, fracture patterns, pre-existing anaemia, and co-morbidities (anaemia, heart disease, chronic kidney disease, oral anticoagulant usage) were recorded. The recorded information also included the type of procedure undergone by each patient. Intra-operative tranexamic acid injections were administered to all patients. Results Male patients accounted for 24% (11) and females for 76% (34). The average age was 82.3 years (range: 73-94). In terms of fracture type, 60% (27) were intracapsular and 40% (18) were extracapsular. Iron deficiency anaemia was present in 24% (11), oral anticoagulants in 20% (9), and systemic malignancy in 12% (6) of patients. The mean post-operative hemoglobin level during endoscopy referral was 7.3 g/dL. Endoscopy revealed normal findings in 60% (27), esophagitis/gastritis in 20% (8), and hiatus hernia in 16% (7) of patients. No patients were diagnosed with active gastrointestinal bleeding or malignancy as the cause of post-operative hemoglobin drop. Conclusion The study did not show evidence of any gastrointestinal bleeding in patients with resistant and refractory post-operative anaemia following fractured neck of femur surgery using endoscopy procedure.The value of such difficult, expensive and time-consuming procedure may be reviewed further.

On use of animal models.

Human pregnancy, critical for our species survival, is inefficient and prone to complications such as infertility, spontaneous miscarriages and preeclampsia (PE). Immunological factors may be important as the embryo is 50% paternal and foreign to the mother. Mouse pregnancy models, and in particular the murine CBA/J x DBA/2 mating combination, has been widely used to investigate mechanisms causing and preventing partner-specific recurrent miscarriages (RM) and PE. Occult losses can represent T cell-mediated rejection, and antigen-specific regulatory T cells (Tregs) with classical αβ T cell receptors (TcR) activated by semen antigens at the time of mating are protective. If there is no occult loss, an inadequate Treg response can also predispose to RM. In RM, proinflammatory cytokines from natural killer (NK)-type cells and macrophages of the innate immune system are responsible and cells with γδ TcR protect via release of TGF-β-type molecules. Immunization of abortion-prone female CBA/J mice or administration of cell-associated or soluble CD200, an immune check point inhibitor, can prevent abortions by augmenting uterine decidual suppressor cell activity. Human studies suggest that is also true in couples with RM. Environmental activators of the innate immune system, such as bacterial LPS and stress, can cause abortions as well as occult losses. The endogenous level of Tregs and activation of Tregs specific for the male H-Y antigen may determine success rates and alter the male:female birth ratio. Intralipid alters LPS clearance, prevents abortions in the CBAxDBA/2 model, and is effective in increasing live birth rates in couples undergoing IVF treatment.

Does Renal Function Remain Stable after Puberty in Children who underwent Ureteral Reimplantation due to Ureterovesical Junction Obstruction?

Ureteric reimplantation due to ureterovesical junction (UVJ) obstruction enjoys high success in the short term. However, renal function after reimplantation must accommodate the numerous changes in the pediatric urinary tract that occur along with child development that may theoretically cause an occult loss of renal function. The purpose of this study was to evaluate whether improved renal function after ureter reimplantation for antenatal diagnosed UVJ obstruction remains stable after puberty. Twenty-one children who underwent open reimplantation using Politano-Leadbetter technique were followed until they completed puberty. Mean age at surgery was 14.3 months (range: 3-60 months). Five (23.8%) of 21 children had right hydronephrosis, 13 (61.9%) had left hydronephrosis, and 3 (14.3%) had bilateral hydronephrosis. The Society for Fetal Urology (SFU) level of the hydronephrosis was 3 (47.6%) in 10 children and 4 (52.4%) in remaining 11. Fourteen (66.6%) patients had poor renal function upon surgery and the remaining seven (33.4%) patients had moderate renal function. The mean renal function upon operation was 28 ± 4.3 (mean ± standard deviation [SD]). Reimplantation led to the increase in the RRF in the short-term period from 28 ± 4.3% prior to the surgery to 36.4 ± 5% (p < 0.001) in all patients and remains stable 35 ± 5% after puberty in all the reviewed patients. Our data demonstrate for the first time that successful ureteral reimplantation following antenatal diagnosis of UVJ obstruction is associated with an improvement in renal function, not only during short- and midterm follow-up but also allows preserving the renal function throughout the puberty period.

Clinical analysis of occult blood loss in treatment of proximal humeral fracture with shoulder hemiarthroplasty

Objective To determine the total bleeding,occult bleeding,and anticoagulant use in treatment of proximal humeral fracture combined with shoulder hemiarthroplasty in order to provide necessary data for the clinical treatment.Methods Sixty-one patients with proximal humeral fracture undergone shoulder hemiarthroplasty from July 2004 to July 2013 were retrospectively analyzed for preoperative and postoperative blood routine and intraoperative and postoperative blood loss.Results For all 61 patients,total blood loss was (981.3 ± 341.5)ml and hidden loss (525.7 ± 244.6)ml,with mean occult bleeding making up 54％.Anticoagulant was used in 20 patients,with occult blood loss of (616.0 ± 267.8) ml,accounting for 59％ of total bleeding [(1 051.3 ± 402.1) ml].Anticoagulant therapy was not initiated for 41 patients and their occult loss was (481.6 ± 222.7) ml,accounting for 51％ of total bleeding [(947.2 ± 307.4) ml].More occult bleeding was observed in patients with anticoagulant therapy than those without (P ＜ 0.05).Conclusions Occult loss predominates the total blood loss during shoulder hemiarthroplasty for patients with proximal humeral fracture,which is worthy of special attention.Moreover,further occult bleeding is observed in patients treated with anticoagulant therapy. Key words: Shoulder fractures; Arthroplasty, replacement; Blood loss, surgical; Anticoagulant drug

ORIGINAL ARTICLE: Prevention of Spontaneous Abortion in the CBA × DBA/2 Mouse Model by Intravaginal TGF‐β and Local Recruitment of CD4+ 8+ FOXP3+ Cells

ProblemActivation of latent transforming growth factor (TGF)‐β in seminal plasma has been suggested by Robertson et al. to promote maternal tolerance to paternal antigens. A possible consequence reported by Tremellen et al. is increased pregnancy rates in women undergoing IVF. A decreased spontaneous abortion rate has also been postulated. Seminal plasma contains many factors besides TGF‐β, and a critical test of the hypothesis was required. The purpose of the present study was to directly test the effect of pure TGF‐β.Method of studyPharmaceutical grade bioactive TGF‐β3 with a bovine serum albumin (BSA) carrier 0.1–1% in phosphate‐buffered saline (PBS) was given into the vaginal tract of CBA/J female mice at the time of mating with DBA/2 males. One microgram Salmonella enteritidis lipopolysaccharide was given intraperitoneally to augment occult losses and spontaneous resorptions assessed on day 13.5 of pregnancy. The effect of TGF‐β3 on recruitment of lymphomyeloid cells to the vaginal wall and vaginal lumen of unmated mice in estrus was assessed using immunohistochemistry and flow cytometry.ResultsTwo nanogram of intravaginal TGF‐β3 in 0.1% BSA–PBS or 20 ng in 1% BSA–PBS reduced abortion rates. Protection was comparable to that achieved by immunization with BALB/c spleen cells. Fraction V BSA, a binder of TGF‐βs, had some activity, and could reduce availability of added TGF‐β3. CD11c dendritic cells, CD3+ T cells, and CD25+ cells were recruited to the vaginal wall by 48 hr after TGF‐β3 treatment, and cellularity of vaginal exudates increased. Foxp3+ cells were present in increased numbers, and appeared to be CD8+ and CD4+ 8+. Semen, but not TGF‐β3, stimulated a physiological polymorphonuclear leukocyte exudate.ConclusionIntravaginal bioactive TGF‐β3 can enhance success of pregnancy in vivo in an established model of abortion. The result could be explained by the independent ability of TGF‐β to promote a regulatory T‐cell response.

LPS‐Induced Occult Loss in Mice Requires FGL2

FGL2 prothrombinase is required for spontaneous abortion (resorptions) in the CBA x DBA/2 model, and for abortions in C57Bl/6 (B6) mice triggered by Salmonella enteritidis lipopolysaccharide (LPS). Unlike abortions, occult losses in B6 mice, which begin before gestation day 9.5 in mice, do not require the tumor necrosis factor-alpha receptor type 1, and may be triggered by either Salmonella enteritidis or Escherichia coli LPS. Heterozygous matings of fgl2+/-xfgl2+/- B6 mice also have a high spontaneous occult loss of fgl2-/- and to a lesser extent, fgl2+/- embryos caused by hemorrhage between trophoblast and Reichert's membrane. However, the frequency of such losses appears to vary among breeding periods and between laboratories. We tested the hypothesis that FGL2-deficient embryos were uniquely susceptible to LPS by treating B6 fgl2+/-xfgl2+/- heterozygous matings with 2 microg E. coli LPS intraperitoneally on day 6.5 of pregnancy. Progesterone 2 mg in 100 microL sesame oil was administered subcutaneously at the same time to ensure that the effects of the LPS were not because of suppression of ovarian hormone production. PCR DNA genotyping was performed on embryos at day 13.5 of pregnancy, or after parturition. Surprisingly, we found that LPS caused occult loss of fgl2+/+, and to a lesser extent fgl2+/- embryos, both at term and by PCR typing of embryos at gestation day 13.5, and these losses obscured the effect of fgl2 knockout. Spontaneous loss of fgl2-/- embryos may relate to adhesion effects, whereas fgl2+/+ embryos are susceptible to LPS-induced loss; fgl2+/- embryos may be affected by both mechanisms. Antagonizing FGL2 could prevent occult pregnancy loss in some human and animal situations.

The fgl2 prothrombinase/fibroleukin gene is required for lipopolysaccharide-triggered abortions and for normal mouse reproduction.

Increased fgl2 prothrombinase activity in maternal decidua and fetal trophoblasts may trigger abortions by proinflammatory cytokines induced by bacterial lipopolysaccharide (LPS) in mice and is implicated in human recurrent miscarriages and pre-eclampsia. Defining the physiological and pathological role of the fgl2/fibroleukin gene required an fgl2-knockout mouse and data on normal pattern of fgl2 expression during pregnancy. Expression of fgl2 protein was determined by immunostaining with specific antibody. Fgl2 knockout mice were generated and typed by PCR for presence of the altered gene. Immunostaining of timed CBAxDBA/2 mouse matings in a low-abortion-rate colony showed a distinct pattern of development of fgl2 protein expression in maternal decidua, and in embryonic tissues in early pregnancy. Outbred (mixed background) heterozygous fgl2 +/-x+/- matings with a similar low abortion rate showed selective occult loss of both +/- and, to a greater extent, -/- embryos prior to gestation day 11.5, in association with haemorrhage at the anti-mesometrial pole of fgl2-deficient embryo. LPS injected on day 6.5 caused classical abortions at mid-pregnancy in fgl2 +/+x+/+ matings, but not -/-x-/- matings. Physiological expression of fgl2 in fetal trophoblast may prevent occult loss in early pregnancy, along with other coagulation factors, but fgl2 expression is required for LPS to induce abortion pathology.

Ca ++ channel-blocking drugs in shock and trauma: New approaches to old problems?

The development of drugs that inhibit Ca++ influx through voltage-regulated cell membrane channels of excitable cells represents a new pharmacodynamic addition to the therapy of cardiovascular disorders. These drugs, the Ca++ channel-blocking agents, have important therapeutic roles in the management of exertional and variant angina and also in the treatment of certain types of supraventricular tachyarrhythmias. In addition, a rapidly expanding body of evidence indicates that these compounds also may exert beneficial actions in various other cardiovascular-related disorders, including different forms of shock and trauma. Theoretically, beneficial effects of Ca++ channel blockade may be explained by either a direct reduction of pathologic Ca++ overload in injured cells or, indirectly, by vasodilation and hemodynamic improvement in tissue perfusion-oxygen demand relationships. Many questions remain unanswered, however, and recent experimental studies have questioned the routine use of these drugs in shock or trauma. Furthermore, the propensity for hypotensive and cardiodepressant actions of Ca++ channel blockade may well be enhanced in patients with preexisting or occult loss of myocardial contractile reserves. These complexities should be assessed carefully before Ca++ channel-blocking drugs are used in the treatment of shock states.

Aspirin and Gastric Hemorrhage

Aspirin-induced bleeding from the gastrointestinal tract manifests itself in two forms: the frequent occult loss of blood which reportedly¹occurs in 70% of patients taking repeated doses of aspirin, and the uncommon overt hemorrhage. Two mechanisms have been implicated in the causation of the occult bleeding: local irritation of the gastric mucosa and hemostatic disturbance. The former—evidenced by mucosal congestion and by accumulation of DNA in gastric washings due to excessive epithelial shedding—is unrelated to the presence of hydrochloric acid.²The hemostatic abnormality is essentially that of prolonged bleeding time, probably caused by reduction in platelet stickiness.³ Whereas no intrinsic pathologic lesion of the gastrointestinal tract need be present to account for covert bleeding induced by aspirin, over hemorrhage in patients not suffering from a blood dyscrasia has been described only in association with peptic ulcer or esophagitis. To these known underlying lesions has now been added

Idiopathic thrombocytopenic purpura: Report of a case

A résumé is presented of idiopathic thrombocytopenic purpura. It is believed that there is excessive destruction of platelets by the spleen; that a substance is elaborated by the spleen which suppresses the formation of platelets from megakaryocytes in the bone marrow; that the existing capillary fragility requires more blood platelets to repair this defect. The diagnosis depends on decrease in the number of circulating platelets, prolonged clot retraction time, normal bone marrow except for occasional megakaryocytosis with agranularity of the cytoplasm of the megakaryocytes, and absence of known causative factors. The symptoms are caused by increased capillary permeability with repeated subcutaneous or submucosal hemorrhages varying from petechiae to large ecchymotic areas. There may be severe menorrhagia or prolonged occult loss of blood resulting in secondary anemia with concomitant bone marrow changes. The treatment is both medical and surgical.