Appendectomy during pregnancy: rates, safety, and outcomes over a five-year period. A hospital-based follow-up study.

INTRODUCTION: Appendicitis is the most common acute abdominal complication during pregnancy. If appendix perforation occurs there is an increasing risk of preterm delivery and other pregnancy complications. OBJECTIVE: To assess the outcome of pregnancy after appendectomy, the mode of surgery used, appendectomy rates, and complications. METHODS: A prospective cohort study of pregnant women with, or without, appendectomy at South Stockholm General Hospital, December 2015 to February 2021 in a setting where pregnant women are prioritized for surgery and laparoscopic surgery was standard of care in first half of pregnancy. Data on preoperative imaging, surgical method, intraoperative findings, microscopic findings, hospital stay, pregnancy, and 30-day complications were prospectively recorded in a local appendectomy register. A non-pregnant control group was gathered comprising women of fertile age in the same study interval. RESULTS: During the study period 50 pregnant women, of whom 44 gave birth, underwent appendectomy of 38 199 women giving birth. There were no differences between women with or without appendectomy in proportion of preterm delivery (4.5% vs. 5.6%), small-for-gestational age (2.3% vs. 6.2%), or Cesarean delivery (18.2% vs. 20.4%). The rate of appendix perforation was 19% in non-pregnant control group compared to 12% among pregnancy. There was no case of perforated appendix in the second half of pregnancy. However, women with gestational age > 20 weeks more frequently had an unaffected appendix compared to those operated ≤ 20 gestational weeks (4/11 vs. 2/39, p = .005). Laparoscopic surgery was used in 97% of non-pregnant control group, 92% of appendectomies ≤ 20 weeks gestation, and in 27% >20 weeks. As compared to first half, the appendectomy rate was three times lower during the second half of pregnancy. Pregnant women had priority for surgery < 6 h compared to < 24 h among non-pregnant women, this resulted in a shorter time-to-surgery among pregnant women (p < .001). CONCLUSION: Routine laparoscopic surgery and time priority for pregnant surgery is associated with a low risk of perforation, preterm birth and other complications. However, a low threshold for surgery may increase the risk of a negative exploration.

High prevalence of an active human cytomegalovirus infection in patients with colonic diverticulitis.

BACKGROUND: Diverticulitis affects 10% of the western population and is characterized by microscopic inflammation of the colon. Increasing evidence suggests that human cytomegalovirus (HCMV) is an important pathogen in various inflammatory diseases. We hypothesized that HCMV contributes to the progression of diverticulitis, especially in immunocompromised patients in whom HCMV is a significant pathogen. OBJECTIVES: To determine if HCMV is associated with diverticulitis and with an increased frequency of diverticulitis complications. STUDY DESIGN: We examined the prevalence of an active HCMV infection in 23 patients with diverticulitis. Serum samples were analyzed for the presence of HCMV-IgG and HCMV-IgM antibodies in 11 of these patients. Immunohistochemistry was used for detection of HCMV early antigens in intestinal paraffin tissue sections obtained from the diverticulitis patients. RESULTS: HCMV-early proteins could be detected in intestinal cells in 16/23 (69.6%) patients with diverticulitis. All of the 11 patients with serum samples were HCMV-IgG positive and 2 of these were also HCMV-IgM positive. CONCLUSION: Active HCMV infection is frequently associated with diverticulitis and could contribute to the inflammatory process characteristic of diverticulitis.

Pancreatic carcinoma incidence and survival in Sweden in 1980-2000: a population-based study of 16,758 hospitalized patients with special reference to different therapies.

AIMS: The purpose of this study was to analyze the incidence and survival of pancreatic carcinoma in Sweden during 1980-2000. METHODS: In this population-based study the patients were identified in the Swedish Hospital Discharge Register and Cancer Register. Data were matched with those in the Register of Causes of Death in Sweden, and 16,758 patients were identified. RESULTS: During the studied period, 1819 patients underwent pancreatic resection, 7457 were treated with palliative procedures and, in 7482, no intervention was carried out. The incidence of pancreatic carcinoma in Sweden for men dropped from 16 per 100,000 at the beginning of the period to 8 per 100,000 in the year 2000. Corresponding figures for women were 12 and 7, respectively. Patients who underwent pancreatic resection had significantly longer survival compared to the palliative procedure or no-intervention groups (p<0.001). After 12 months 49.7% of the resected patients were alive while the corresponding survival in the palliative procedure and no-intervention groups were 13.6% and 11.9%, respectively. The five-year survival rate after resection was 10.8%. In the resection group survival improved over time (p<0.001) and women survived longer than men (p<0.01), which was not the case in the palliative procedure or no-intervention groups. CONCLUSIONS: During the study period, the incidence of pancreatic carcinoma in Sweden decreased markedly. The resection rate increased and only in this group of patients an improved survival was noted over time. The survival was the same for patients who underwent palliative interventions as for those who only received supportive care.

Heteroaryl-fused 2-phenylisothiazolone inhibitors of cartilage breakdown.

The synthesis, biological evaluation, and structure-activity relationships of a series of N-phenyl heteroaryl-fused isothiazolones are described. These isothiazolones have been shown to exhibit potent, dose-dependent inhibition of IL-1 beta-induced breakdown of proteoglycan in a cartilage organ culture assay. This effect is likely due to inhibition of MMP activation and a consequent reduction in MMP activity following IL-1 beta stimulation. Thus these compounds potentially represent simple, non-peptidic disease-modifying agents for the treatment of arthritic diseases. To examine the effects of structure on in vitro activity, three general features of the molecules were varied, substituents on the pendant N-phenyl group, the position of ring fusion to the isothiazolone, and substituents on the fused ring peri to the isothiazolone sulfur.

Design and synthesis of isoxazoline derivatives as factor Xa inhibitors. 1.

Thrombosis is a major cause of mortality in the industrialized world. Therefore, the prevention of blood coagulation has become a major target for new therapeutic agents. One attractive approach is the inhibition of factor Xa (FXa), the enzyme directly responsible for prothrombin activation. We report a series of novel biaryl-substituted isoxazoline derivatives in which the biaryl moiety was designed to interact with the S(4) aryl-binding domain of the FXa active site. Several of the compounds herein have low nanomolar affinity for FXa, have good in vitro selectivity for FXa, and show potent antithrombotic efficacy in vivo. The three most potent compounds (33, 35, and 37) have inhibition constants for human FXa of 3.9, 2.3, and 0.83 nM, respectively, and ID(50)'s ranging from 0.15 to 0.26 micromol/kg/h in the rabbit arterio-venous thrombosis model.

Discovery of an orally active series of isoxazoline glycoprotein IIb/IIIa antagonists.

Using isoxazoline XR299 (1a) as a starting point for the design of highly potent, long-duration GPIIb/IIIa antagonists, the effect of placing lipophilic substituents at positions alpha and beta to the carboxylate moiety was evaluated. Of the compounds studied, it was found that the n-butyl carbamate 24u exhibited superior potency and duration of ex vivo antiplatelet effects in dogs. Replacement of the benzamidin-4-yl moiety with alternative basic groups, elimination of the isoxazoline stereocenter, and reversal of the orientation of the isoxazoline ring resulted in lowered potency and/or duration of action.

A European multicenter study of chronic graft-versus-host disease. The role of cytomegalovirus serology in recipients and donors--acute graft-versus-host disease, and splenectomy.

A group of 466 leukemic bone marrow transplanted patients were reported from 17 European bone marrow transplantation teams. Of these, 285 survived more than 3 months and could be evaluated for chronic GVHD. The cumulative incidence of chronic GVHD was 32% two years after BMT. The following factors were statistically significantly associated with chronic GVHD in bivariate analysis: high donor and recipient age, splenecacute GVHD, pretransplant seropositivity to CMV among the recipients and the donors, and donor seropositivity to 3 or 4 different herpesviruses, compared with 0-2, prior to BMT. In multivariate analysis pretransplant recipient CMV seropositivity in combination with donor CMV seropositivity prior to BMT (P = 0.0006), a previous grade II-IV acute GVHD (P = 0.001), and splenectomy (P = 0.01) were significantly associated with chronic GVHD. Thus, in addition to acute GVHD, CMV immune donor cells may be triggered by latent CMV in the recipient, which may play a role in the triggering of chronic GVHD. The possible role of splenectomy in GVHD is also discussed.

Pretransplant herpesvirus serology and acute graft-versus-host disease.

Logistic regression was used to analyze the influence of pretransplant herpesvirus antibodies, in both patients and donors, on the development of acute graft-versus-host disease in 111 consecutive HLA-identical bone marrow recipients. In bivariate analysis, recipient seropositivity for cytomegalovirus (P = 0.01), donor seropositivity for herpes simplex virus (P = 0.02), and low bone marrow cell dosage (P less than 0.05) were associated with a high incidence of grade II-IV acute GVHD. In multivariate analysis the P values were P less than 0.05 for a positive recipient CMV serology and P = 0.07 for a positive donor HSV serology. Positive serology for 1-2 herpes-viruses among recipients or donors both resulted in a 12% incidence of grade II-IV acute GVHD. Positive serology for 3-4 herpesviruses among patients or donors resulted in an incidence of 32% and 38% of acute GVHD, respectively (P less than 0.05). It is concluded that recipient and donor pretransplant herpesvirus immunity can be used to calculate the risk of moderate-to-severe acute GVHD.

Cytomegalovirus DNA in peripheral blood leukocytes and plasma from bone marrow transplant recipients.

Granulocytes, monocytes, and T- and B-lymphocytes were separated from 28 blood samples collected from 5 bone marrow transplant (BMT) recipients. About 40% of granulocyte, monocyte, and B-lymphocyte samples were CMV DNA-positive by polymerase chain reaction in recipients with cytomegalovirus (CMV) infection. CMV DNA was rarely detected in separated T-lymphocytes. Within each of the simultaneously separated paired samples, there were several with single positive cell subtypes. Monocytes, granulocytes, and B-lymphocytes were the single positive samples in some instances. Thus, it is important to have all of the different cell subtypes present in samples for detection of CMV DNA in peripheral blood. We also studied the appearance of CMV DNA in plasma and peripheral blood leukocytes (PBLs) from 351 blood samples collected from 30 BMT recipients during a follow-up period of at least 3 months after BMT. All cell subtypes were represented in the PBL samples. In the 13 recipients who developed symptoms possibly associated with CMV infection or CMV disease, a correlation with the detection of CMV DNA in < or = 2 x 10(5) PBLs was found. In PBLs from 11 of the 13 BMT recipients, CMV DNA was detected before the onset of symptoms. CMV DNA was not detected in < or = 2 x 10(5) PBLs from recipients without CMV infection. The virus load in PBLs decreased during ganciclovir treatment. Nine of the 13 recipients displayed PCR-positive plasma samples, and CMV DNA was detected frequently after the onset of symptoms.

Variables predicting deep fungal infections in bone marrow transplant recipients.

Deep fungal infections (FI) were diagnosed in 27 out of 209 consecutive bone marrow transplantation (BMT) recipients. Autopsy verified that the incidence of deep FI was 10% and the overall incidence was 13%. Using bivariate logistic regression analysis at the time of BMT, high recipient age (p = 0.003), low bone marrow cell dose (p = 0.007), recipient cytomegalovirus (CMV) seropositivity (p = 0.009) and splenectomy (p = 0.03) were significant risk factors for deep FI. In multivariate analysis, splenectomy (p = 0.008), recipient CMV seropositivity (p = 0.01) and low bone marrow cell dose (p = 0.01) held as significant. At 30 days post-BMT anti-thymocyte globulin treatment (p = 0.0006) and graft-versus-host disease grade II-IV (p = 0.005) were significant risk variables in bivariate logistic regression analysis and Fisher's exact probability test. Patients with these risk factors are candidates for treatment with antifungal drugs when they suffer from leukopenia and unclear fever.

Markedly increased serum erythropoietin levels following conditioning for allogeneic bone marrow transplantation.

Serum erythropoietin (EPO) levels were measured by radioimmunoassay in 36 patients undergoing allogeneic bone marrow transplantation (BMT). Serum EPO levels before conditioning treatment for BMT were generally higher than the levels obtained from healthy controls (49 +/- 17 (SEM) and 17 +/- 0.6, respectively). One day prior to BMT, after conditioning by chemotherapy with or without total body irradiation, the mean EPO level was markedly elevated (218 +/- 23 U/l, p less than 0.001) and reached to its highest level at 1 week post-BMT (269 +/- 40 U/l). Although, the EPO levels were significantly lower at 1 month (98 +/- 24 U/l, p less than 0.001), they were still elevated up to 3 months post-BMT, after which they gradually normalized. Patients given methotrexate and cyclosporine for prophylaxis against graft-versus-host disease (GVHD) had significantly lower EPO levels during the first 3 months post-BMT than patients transplanted with T cell-depleted marrow (p less than 0.05). Patients with post-transplant nephrotoxicity had lower, though not statistically significant, EPO levels than patients with normal renal function (p = 0.07). Acute GVHD and number of blood transfusions had no influence on serum EPO levels after BMT.

Risk factors for acute graft-versus-host disease in 291 consecutive HLA-identical bone marrow transplant recipients.

We analysed 35 risk factors for acute GVHD in 291 consecutive recipients of HLA-identical sibling marrow transplants from 1975 to 1993. Of these, 16% developed moderate-to-severe acute GVHD following transplantation. In multivariate analysis, GVHD prophylaxis with monotherapy (MTX or CsA) (P = 0.015) seropositivity for several herpes viruses in the donor (P = 0.015) and seropositivity for CMV in the recipient (P = 0.037) before the transplants as well as early engraftment (P = 0.016), were the principal risk factors for GVHD. A high serum TNF-alpha level during conditioning therapy was also a significant risk factor in 75 recipients (P = 0.005). The risk of grades II-IV acute GVHD increased with the number of risk factors. Thus the cumulative incidence of acute GVHD was 1%, if no risk factor was present, 4% with one, 9% with two, 21% with three and 44% in patients with four risk factors. Factors reported to correlate with acute GVHD, such as age, diagnosis, female donor to male recipient, relative response and donor-responding capacity in MLC, MNS blood group antigen, splenectomy and bone marrow cell dose were not associated with acute GVHD in this study. Five-year survival was 24% in patients with grades II-IV GVHD vs 62% in patients with grades 0-I GVHD (P = 0.0001).

Pretransplant herpes virus serology and chronic graft-versus-host disease.

The influence of pretransplant herpes virus antibodies in patients and donors in the subsequent development of chronic graft-versus-host disease (GVHD) was analysed in 150 consecutive HLA identical bone marrow recipients. The Cox regression bivariate analysis showed that (i) pretransplant seropositivity for cytomegalovirus (CMV) in the patients and the donors, (ii) donor seropositivity for herpes simplex virus and Epstein-Barr virus, (iii) high donor and patient age, (iv) a previous grade II-IV acute GVHD, (v) patients receiving unirradiated donor buffy coat cells post-transplant, (vi) overall CMV infection, (vii) high donor herpes virus load (positive serology for 3-4 herpes viruses versus 0-2), and (viii) high recipient herpes virus load prior to BMT were all associated with a high incidence of chronic GVHD. In Cox regression multivariate analysis, high pretransplant donor herpes virus load (p less than 0.001) and a previous grade II-IV acute GVHD (p = 0.02) were the strongest predictors of chronic GVHD. Thus, herpes virus immune cells in the donated marrow may play a role in the pathophysiology of chronic GVHD.

A role of herpes virus serology for the development of acute graft-versus-host disease. Leukaemia Working Party of the European Group for Bone Marrow Transplantation.

Pretransplant herpes virus serology and acute graft-versus-host disease (GVHD) were studied in 379 leukaemic bone marrow transplant (BMT) recipients and their HLA-identical sibling donors. In logistic multivariate regression analysis pretransplant seropositivity to three or more different herpes viruses among the recipients was the only significant factor associated with grade II-IV acute GVHD (p = 0.03). If this factor was excluded, older donor age (p less than 0.001), absence of T cell depletion (p less than 0.001), pharmacological immunosuppression by monotherapy of methotrexate or cyclosporin versus a combination therapy of both (p = 0.002), and seropositivity to three or more herpes viruses among the donors (p = 0.03) prior to BMT, were also significantly associated with acute GVHD. The data indicate that latent herpes viruses in the host may act as minor histocompatibility antigens or by other means to trigger acute GVHD.

Neutrophil response and microbiological findings around teeth and dental implants.

The aim of this study was to compare the neutrophil response, measured as both functional and antigenic elastase, around teeth and titanium implants and to relate these findings to the microbiota. The 31 patients included in the study had been treated successfully for total or partial edentulism with titanium implants. Crevicular fluid and microbiological samples were taken from 3 sites: 1) crevices around teeth and 2) implants in 16 partially edentulous patients and 3) crevices around implants in 15 edentulous patients. All sites sampled showed similar degrees of inflammation assessed by gingival index and total protein concentration. The samples were analyzed for elastase activity and immunoreactive elastase. The elastase activity was significantly higher in crevices surrounding implants in partially edentulous patients compared with implants in edentulous patients. The antigenic elastase showed no difference among the 3 sites. Gram-positive cocci were the main bacterial species in all 3 groups. Edentulous patients tended to have lower frequency of black pigmenting anaerobes. No correlation of analyzed bacteria and elastase activity was found between the 3 sites. This study indicates that, despite a similar appearance of clinical parameters and absence of significant differences in the microbiota, the inflammation around implants in partially edentulous patients induces a stronger neutrophil response than does the inflammation around implants in edentulous patients.

Acute carpal tunnel syndrome caused by peritendinitis calcarea. Case report.

Two women presented with similar symptoms of acute pain in the hand that was diagnosed as acute carpal tunnel syndrome caused by peritendinitis calcarea. Radiological examinations in both cases showed calcifications in the carpal tunnel. Both patients were operated on immediately and the median nerve was decompressed. Both were completely relieved of pain after operation and hand function returned to normal.

Surgical treatment of carpal tunnel syndrome in patients exposed to vibration from handheld tools.

During 1985 at Sabbatsberg Hospital in Stockholm, carpal tunnel decompression was done for 50 men (58 hands) with carpal tunnel syndrome (CTS). In 1988 2.5 to 3 years after the operations, a questionnaire about their present health was answered by 43 men (50 hands). In 10/17 (59%) hands exposed to vibrations and 26/33 (79%) not exposed, carpal tunnel decompression had resulted in no recurrence of neurological symptoms at follow up. Preoperative signs of neurophysiological dysfunction of the ulnar nerve, which might indicate a more widespread neuropathy, did not correlate with poor postoperative function of the median nerve. We recommend that patients with carpal tunnel syndrome should be operated on, whether or not they have been exposed to vibration.

[Surgery cures numbness of the hand. Long-term follow-up of carpal tunnel decompression]. / Operation botar domningar i handen. Långtidsuppföljning av karpaltunnelklyvningar.

One hundred and ninety-one hands with suspected carpal tunnel syndrome (CTS) were treated with surgical decompression of the median nerve. In a retrospective analysis 2.5-3 years later, an inquiry was carried out by questionnaire and the patients' records were examined to evaluate the final outcome. The questionnaire was answered by all 158 still living patients (ie, 175 hands), of whom 91 per cent reported numbness in the hand to have been completely relieved after surgery, while 23 per cent had had a recurrence of numbness, or other hand problems not clearly related to CTS, though just under half of this 23 per cent reported their symptoms to be milder than prior to operation. Thus, 2.5-3 years after surgical intervention, 85 per cent of the patients had recovered completely or improved; and 96 per cent were satisfied with the outcome. To conclude, surgical treatment of CTS is a technically simple operation with good final results.

[More precise indications for fluid therapy during transportation to hospital are required]. / Tydliga indikationer krävs för att ge vätska under transport till sjukhus.

Although early intravenous fluid therapy for haemorrhage and shock is usually given before arrival at the hospital, its value is unclear and more precise indications are needed. The indications will take into account such factors as transport time, volume and type of bleeding, and the presence or absence of concomitant head injury. Fluid resuscitation can be omitted if transport time is less than 30 min, but may be beneficial if it is more than 30 min. Choice of infusion rate should be guided by the estimated risk of re-bleeding when haemorrhage is uncontrolled, and by cerebral perfusion where severe head injury is present.

[Increased number of knife assaults inspite of the legislation. Record of injuries among 399 patients]. / Fler knivöverfall trots knivlagen. Skadepanorama hos 399 knivhuggna patienter.

From January 1985 to September 1993, 399 patients (368 men and 31 women), median age 28 years (mean 31.1, range 16-71 years), were admitted with stab wounds due to assault. The number of stab wounds per patient was one (N = 268 patients), two (N = 63), three (N = 31), four (N = 15), five (N = 7), or more than five (N = 15). The series as whole (N = 399) accounted for 543 sites of injury. Upper extremity wounds were the most frequent (35 per cent); of 188 arm injuries, 60 per cent were in the left arm. The next most frequent site was the head and neck region (N = 105; 12 per cent), followed by the chest (N = 75; 14 per cent), abdomen (N = 66;12 per cent), lower extremities (N = 59;11 per cent), back (N = 48;9 per cent), and the male genitalia (N = 2;0.4 per cent). Ninety-five major operations were performed in 74 patients. Seven patients died, and 40 had somatic or cosmetic life-time sequelae.