Combined effect of age and body mass index on postoperative mortality and morbidity in laparoscopic cholecystectomy patients.

Background: Previous studies have assessed the impact of age and body mass index (BMI) on surgery outcomes separately. This retrospective cohort study aimed to investigate the combined effect of age and BMI on postoperative mortality and morbidity in patients undergoing laparoscopic cholecystectomy. Methods: Data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database for laparoscopic cholecystectomy patients between 2008 and 2020 were analyzed. Patient demographics, functional status, admission sources, preoperative risk factors, laboratory data, perioperative variables, and 30-day postoperative outcomes were included in the dataset. Logistic regression was used to determine the association of age, BMI, and age/BMI with mortality and morbidity. Patients were stratified into different subcategories based on their age and BMI, and the age/BMI score was calculated. The chi-square test, independent sample t-test, and ANOVA were used as appropriate for each category. Results: The study included 435,052 laparoscopic cholecystectomy patients. Logistic regression analysis revealed that a higher age/BMI score was associated with an increased risk of mortality (adj OR 13.13 95% CI, 9.19-18.77, p < 0.0001) and composite morbidity (adj OR 2.57, 95% CI 2.23-2.95, p < 0.0001). Conclusion: Older age, especially accompanied by a low BMI, appears to increase the post-operative mortality and morbidity risks in laparoscopic cholecystectomy patients, while paradoxically, a higher BMI seems to be protective. Our hypothesis is that a lower BMI, perhaps secondary to malnutrition, can carry a greater risk of surgery complications for the elderly. Age/BMI is strongly and positively associated with mortality and morbidity and could be used as a new scoring system for predicting outcomes in patients undergoing surgery. Nevertheless, laparoscopic cholecystectomy remains a very safe procedure with relatively low complication rates.

Case Report: COVID-19 Infection of a Transplanted Heart Simulating Cellular Rejection.

Contemporary reports showed that solid organ transplantation patients who contract SARS-CoV-2 infection have a high mortality rate. There are sparse data about recurrent cellular rejections and the immune response to the SARS-CoV-2 virus in patients after heart transplantation. Herein, we report a case of a 61-year-old male post-heart transplant patient who tested positive for COVID-19 and developed mild symptoms 4 months after transplantation. Thereafter, a series of endomyocardial biopsies showed histologic features of acute cellular rejection despite optimal immunosuppression, good cardiac functions, and hemodynamic stability. Demonstration of SARS-CoV-2 viral particles by electron microscopy in the endomyocardial biopsy confirmed the presence of the virus in the foci of the cellular rejection, pointing to a possible immunologic reaction to the virus. To our knowledge, there is limited information regarding the pathology of COVID-19 infection in immunocompromised heart transplant patients, and there are no well-established guidelines for treating such patients. Based on the demonstration of SARS-CoV-2 viral particles within the myocardium, we concluded that myocardial inflammation visible on endomyocardial biopsy might be attributed to the host's immune response to the virus, which mimics acute cellular rejection in newly heart transplanted patients. We report this case to increase awareness of such events post-transplantation and to add to knowledge regarding the management of patients with ongoing SARS-CoV-2 infection that proved to be challenging.

Chances of Finding Matched Unrelated Donors for Saudi Patients in Need of Hematopoietic Stem Cell Transplantation.

Finding HLA-matched donors for patients in need of hematopoietic stem cell transplantation (HSCT) stands a better chance in their own ethnic group. This information led many nations to establish unrelated stem cell donor registries. We started our Saudi Stem Cell Donor registry (SSCDR) in 2011. The calculated donor pool size was nearly 1 million donors to find a matched donor for every patient. So far we have recruited 75,145 donors. In this exercise we attempted to investigate the chances of finding a matched donor for Saudi patients in need of HSCT. A total of 445 patients were recruited for this study. Donor searches were carried out locally and internationally using Prometheus software and World Marrow Donor Association Search and Match Service, respectively. Only 24% of the patients found a matched donor in our registry, 12% found a donor in other registries, making it a total of 36% of our patients who have the chance to find a full 10/10 HLA-matched donor. However, when we included 9/10 and 8/10 with the full matched donors, the chances go up to 83%. The top scoring registries for number of patients finding 10/10 matched donors were SSCDR (108), Deutsche Stammzellspenderdatei Nabelschnurblut (n = 52), King Faisal Specialist Hospital & Research Centre Stem Cell Donor Registry (n = 52), NMDP-National Marrow Donor Program/Be The Match (n = 43), TURKOK-Turkish Stem Cell Coordination Centre (n = 39), DKMS United Kingdom (n = 24), and Ezer Mizion Bone Marrow Donor Registry (n = 20). The patient who found the highest number of donors in international registries carried the European haplotype A1-B8-DR3; a total of 272 donors were found, and none of them were from our registry. Patients with the highest matched donor numbers in SSCDR carried haplotypes that were not common in international registries. Having a local registry increases the chances of finding a matched donor for our patients; however, international registries can still add to the chances of finding matched donors. Increasing our donor pool will increase chances of our patients finding a matched donor.

Inflammatory Response and Phenotyping in Severe Acute Respiratory Infection From the Middle East Respiratory Syndrome Coronavirus and Other Etiologies.

OBJECTIVES: In this study, we evaluated the inflammatory response in patients with severe acute respiratory infection due to the Middle East respiratory syndrome and non-Middle East respiratory syndrome and assessed the presence of distinct inflammatory subphenotypes using latent class analysis. DESIGN: Prospective cohort study. SETTING: A tertiary care ICU in Riyadh, Saudi Arabia. PATIENTS: Consecutive critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We measured cytokines on days 1, 3, 7, and 14 of ICU stay. We included 116 patients (40 with Middle East respiratory syndrome severe acute respiratory infection and 76 with non-Middle East respiratory syndrome severe acute respiratory infection). On ICU day 1, both patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection had higher levels of interleukin-3, interleukin-4, interleukin-6, interleukin-8, interleukin-17A, eotaxin, and epidermal growth factor compared with healthy controls. There were no differences in cytokines over time between patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. Using day 1 cytokine levels, latent class analysis categorized patients into two subphenotypes: subphenotype 1 (n = 74 [64%]) and subphenotype 2 (n = 42 [36%]); the latter had significantly higher levels of interleukin-1ß, interleukin-1ra, interleukin-2, interleukin-6, interleukin-7, interleukin-8, interleukin-10, interleukin-12p70, interleukin-15, interleukin-17A, inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-1ß, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, granulocyte-colony stimulating factor, interferon-α, and interferon-γ. Although baseline characteristics were not different between the two subphenotypes, patients in the subphenotype 2 had higher ICU mortality compared with the subphenotype 1 (18/42 [43%] vs 17/74 [23%]; p = 0.03). CONCLUSIONS: One third of critically ill patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection demonstrated a subphenotype characterized by increased proinflammatory cytokines, consistent with cytokine storm. Further research is needed to examine whether immunomodulators have differential effects based on inflammatory subphenotypes.

HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 Allele and Haplotype Frequencies of 28,927 Saudi Stem Cell Donors Typed by Next-Generation Sequencing.

Human leukocyte antigen (HLA) allele and haplotype frequency distribution varies widely between different ethnicities and geographical areas. Matching for HLA alleles is essential for successful related and unrelated stem cell transplantation. Among the Saudi population, data on HLA alleles and haplotypes are limited. A cross-sectional study was performed on 28,927 bone marrow donors. The most frequent HLA alleles were HLA-A*02:01:01G (20.2%), A*24:02:01G (7.5%); B*51:01:01G (19.0%), B*50:01:01G (12.3%); C*06:02:01G (16.7%), C*07:02:01G (12.2%); DRB1*07:01:01 (15.7%), DRB1*03:01:01G (13.3%); DQB1*02:01:01G (29.9%), DQB1*03:02:01G (13.2%); and DPB1*04:01:01G (35.2%), DPB1*02:01:02G (21.8%). The most frequent HLA-A~C~B~DRB1~DQB1 haplotypes were A*02:01:01G~C*06:02:01G~B*50:01:01G~DRB1*07:01:01G~DQB1*02:01:01G (1.9%) and A*02:05:01G~C*06:02:01G~B*50:01:01G~DRB1*07:01:01G~DQB1*02:01:01G (1.6%). The most frequent HLA-A~C~B~DRB1~DQB1~DPB1 haplotypes were A*02:01:01G~C*15:02:01G~B*51:01:01G~DRB1*04:02~DQB1*03:02:01G~DPB1*04:01:0G (1%) and A*02:01:01G~C*07:02:01G~B*07:02:01G~DRB1*15:01:01G~DQB1*06:02:01G~ DPB1*04:01:01G (0.9%). Based on these haplotype frequencies, we provide forecasts for the fraction of patients with full matching and single mismatched donors for 3 to 6 loci depending on the registry size. With one million donors, about 50% of the patients would find an 8/8 match and 90% a 7/8 match. These data are essential for registry planning, finding unrelated stem cell donors, population genetic studies, and HLA disease associations.

Common, intermediate and well-documented HLA alleles in world populations: CIWD version 3.0.0.

A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well-documented (≥5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.

HLA-A, B, C, DRB1 and DQB1 allele and haplotype frequencies in volunteer bone marrow donors from Eastern Region of Saudi Arabia.

We analyzed HLA allele and haplotype frequencies from donors from the Eastern region of Saudi Arabia. A cross-sectional study was performed on 2405 bone marrow donors from the Eastern region. HLA typing was carried out by sequencing. The most common HLA allele groups were HLA-A*02:01:01G (11.08%), A*01:01:01G (10.40%), HLA-B*52:01:01G (8.79%), B*18:01:01G (8.07%), HLA-C*04:01:01G (17.88%), C*12:03:01G (10.23%), HLA-DRB1*10:01 (14.89%), DRB1*03:01:01G (14.10%), HLA-DQB1*02:01:01G (24.53%) and DQB1*05:01:01G (20.17%). The most frequent HLA-A~ C~ B~ DRB1~ DQB1 haplotypes were HLA-A*01:03~ C*15:05:01G~ B*73:01~ DRB1*10:01:01~ DQB1*05:01:01G (3.11%) and HLA-A*01:01:01G~ C*12:02:01G~ B*52:01:01G~ DRB1*15:02:01~ DQB1*06:01:01G (2.25%). When comparing the allele and haplotype frequencies of the Eastern regions' population to those from the Central region we found significant differences in several allele frequencies including A*01:01:01G (P ≤ 0.0001), B*52:01:01G (P ≤ 0.0001), B*18:01:01G (P = 0.0001), C*12:03:01G (P < 0.0001), DRB1*10:01:01 (P < 0.0001) and DQB1*05:01:01G (P < 0.0001). Our data confirms genetic heterogeneity among the Saudi population.

Identification of the novel HLA-A*23:91N allele in a Saudi individual.

HLA-A*23:91N differs from HLA-A*23:01:01 by a single-nucleotide substitution (G → A) at position 369.

Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection - clinicopathological and ultrastructural study.

AIMS: The pathogenesis, viral localization and histopathological features of Middle East respiratory syndrome - coronavirus (MERS-CoV) in humans are not described sufficiently. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS-CoV infection and represent a base of MERS-CoV histopathology. METHODS AND RESULTS: We analysed the post-mortem histopathological findings and investigated localisation of viral particles in the pulmonary and extrapulmonary tissue by transmission electron microscopic examination in a 33-year-old male patient of T cell lymphoma, who acquired MERS-CoV infection. Tissue needle biopsies were obtained from brain, heart, lung, liver, kidney and skeletal muscle. All samples were collected within 45 min from death to reduce tissue decomposition and artefact. Histopathological examination showed necrotising pneumonia, pulmonary diffuse alveolar damage, acute kidney injury, portal and lobular hepatitis and myositis with muscle atrophic changes. The brain and heart were histologically unremarkable. Ultrastructurally, viral particles were localised in the pneumocytes, pulmonary macrophages, renal proximal tubular epithelial cells and macrophages infiltrating the skeletal muscles. CONCLUSION: The results highlight the pulmonary and extrapulmonary pathological changes of MERS-CoV infection and provide the first evidence of the viral presence in human renal tissue, which suggests tissue trophism for MERS-CoV in kidney.

Lymphocyte recovery is an independent predictor of relapse in allogeneic hematopoietic cell transplantation recipients for acute leukemia.

AIM: To examine the optimal absolute lymphocyte count (ALC) cut-off utilizing receiver operator characteristics (ROC) in addition to graft characteristics associated with early ALC recovery. METHODS: Patients who received T-cell replete peripheral hematopoietic cell transplantation (HCT) for acute leukemia were identified. ALC cut-off was established using ROC analysis and subsequently the cohort was stratified. Time to endpoint analysis and cox regression modelling was computed to analyze outcomes. RESULTS: A total of 72 patients met the inclusion criteria and were analyzed. Optimal ALC cut-off was established to be on day 14 (D14) with ALC > 0.3 × 109/L. At 2 years, cumulative incidence of relapse was 16.9% vs 46.9% (P = 0.025) for early and delayed lymphocyte recovery cohorts, respectively. Chronic graft vs host disease was more prevalent in the early lymphocyte recovery (ELR) group at 70% vs 27%, respectively (P = 0.0006). On multivariable analysis for relapse, ELR retained its prognostic significance with HR = 0.27 (0.05-0.94, P = 0.038). CONCLUSION: ELR is an independent predictor for relapse in patients receiving allogeneic HCT for acute leukemia. ELR was influenced by graft characteristics particularly CD34 count.

Screening panel-reactive antibody negative, single-antigen positive: a case report.

Sensitized patients remain a challenge for successful transplant. Virtual crossmatch is used to determine the presence or absence of donor-specific antibodies. A 60-year-old woman with a negative screening for panel-reactive antibodies (PRA) received an A*11, A*68 type kidney with a negative anti-human globulin/complement-dependent cytotoxicity (AHG-CDC) crossmatch. Her transplant course was complicated by delayed graft function, and she required hemodialysis. On day 8 after receiving the transplant, she had a kidney biopsy that showed features of antibody-mediated rejection/severe acute tubular necrosis, which was treated by plasmapheresis for 5 sessions and intravenous immunoglobulin (2 g/kg). Her serum level of creatinine decreased from 6.7 to 3.6 mg/dL (600-320 µmol/L). Panel-reactive antibody by Luminex was repeated and again was negative. Single-antigen detection was tried next. Surprisingly, A*11:02 came up positive with a mean fluorescence intensity of 9500. High-resolution donor HLA type was A*68:01 and A*11:01. A*11:02 is not part of the screening Luminex PRA whereas the 11:01 allele is. Serologically, HLA-A11 has 2 defined splits, A11.1 and A11.2, which encode A*11:01 and A*11:02, respectively. In this case, the A*11:02 antibody does not seem to be responsible for the increasing creatinine level. However, if the donor had been A*11:02, a humeral rejection would have occurred and been missed by a virtual crossmatch. Thus virtual crossmatch may not work at all times. Screening for PRA by single antigens is suggested even in PRA-negative cases, if only virtual crossmatch is to be used.

Stem cell research and regenerative medicine at King Abdullah International Medical Research Center.

Translation of stem cell research from bench to bedside opens up exciting new therapeutic options for patients. Although stem cell research has progressed rapidly, its clinical applications have not kept pace. We report on the establishment of a stem cell research and regenerative medicine program at King Abdullah International Medical Research Center (KAIMRC). The purpose of this unit is to coordinate advanced stem cell research and translational outcomes with the goal of treating chronic human diseases, such as cancer, diabetes, cardiovascular, neurological, immunological, and liver diseases. Our first step in achieving this goal was to integrate the stem cells and regenerative medicine unit with our umbilical cord blood bank and bone marrow registry. This organizational structure will provide different sources for stem cells for research and clinical purposes, and facilitate our stem cell research and stem cell transplantation program. We are at an early and exciting stage in our program, but we believe that our progress to the international stage will be rapid and have a significant impact.

Novel point mutations and mutational complexes in the enhancer II, core promoter and precore regions of hepatitis B virus genotype D1 associated with hepatocellular carcinoma in Saudi Arabia.

In this study, a cohort of 182 patients [55 hepatocellular carcinoma (HCC) and 127 non-HCC] infected with hepatitis B virus (HBV) in Saudi Arabia was investigated to study the relationship between sequence variation in the enhancer II (EnhII), basal core promoter (BCP) and precore regions of HBV genotype D (HBV/D) and the risk of HCC. HBV genotypes were determined by sequencing analysis and/or enzyme-linked immunosorbent assay. Variations in the EnhII, BCP and precore regions were compared between 107 non-HCC and 45 HCC patients infected with HBV/D, followed by age-matched analysis of 40 cases versus equal number of controls. Age and male gender were significantly associated with HCC (p = 0.0001 and p = 0.03, respectively). Serological markers such as aspartate aminotransferase, albumin and anti-HBe were significantly associated with HCC (p = 0.0001 for all), whereas HBeAg positivity was associated with non-HCC (p = 0.0001). The most prevalent HBV genotype was HBV/D (94%), followed by HBV/E (4%), HBV/A (1.6%) and HBV/C (0.5%). For HBV/D1, genomic mutations associated with HCC were T1673/G1679, G1727, C1741, C1761, A1757/T1764/G1766, T1773, T1773/G1775 and C1909. Age- and gender-adjusted stepwise logistic regression analysis indicated that mutations G1727 [odds ratio (OR) = 18.3; 95% confidence interval (CI) = 2.8-118.4; p = 0.002], A1757/T1764/G1766 (OR = 4.7; 95% CI = 1.3-17.2; p = 0.01) and T1773 (OR = 14.06; 95% CI = 2.3-84.8; p = 0.004) are independent predictors of HCC development. These results implicate novel individual and combination patterns of mutations in the X/precore region of HBV/D1 as predictors of HCC. Risk stratification based on these mutation complexes would be useful in determining high-risk patients and improving diagnostic and treatment strategies for HBV/D1.

HLA-C polymorphisms in two cohorts of donors for bone marrow transplantation.

The typing for HLA-C in transplantation was rather neglected in the past. However, several recent studies have emphasized its role in transplantation and its association with the outcome. Serological typing of HLA-C could identify only a limited number of HLA-C antigens, resulting in a number of HLA-C blanks. This was mainly due to the low expression of surface HLA-C and the small number of available specific anti-sera. Performing molecular methods has identified new HLA-C alleles and filled the blank of most serological typed antigens. In this study, we compared serological and molecular typing of HLA-C in two cohorts of healthy Saudis. Our serological typing method identified HLA-C1-7 with different frequencies, 23.5% of the alleles were not identified and thus defined as blank. Using the SSP molecular method, all samples were typed and all alleles were defined. Both methods showed that C∗07 and C∗06 have the highest frequency in the Saudi population. Our study emphasizes the importance of molecular methods in identifying all possible HLA-C alleles.

Association between antibiotic use and risk of prostate cancer.

The association between antibiotics and risk of cancer has been addressed in different studies, most of which were addressing breast cancer. The objective of this study was to assess the association between antibiotics use and risk of prostate cancer. We carried out a population-based case-control study using data from Saskatchewan Health administrative databases (Canada) between the years 1981 and 2000. Cases identified by the Saskatchewan Cancer Agency were matched to 4 controls, using incidence density sampling. The effect of dosage and timing of antibiotic use, over a minimum of 15 years before diagnosis, on prostate cancer risk was assessed. Number of prescriptions and number of tablets were used as exposure definitions. Moreover, the effect of different classes of antibiotics on prostate cancer was also studied. A total of 4,052 prostate cancer cases and 16,208 matched controls were included in this study. Antibiotics exposure (number of prescriptions) during the period of 1-15 years in the past was significantly associated with an increased risk of prostate cancer; RR = 1.69, 2.61, 2.71, and 2.83 for the 4 quartiles, respectively, p-trend = 0.0001. When number of units was taken as the exposure definition, similar results were found. We did not find any effect of the timing or class of antibiotic exposure on prostate cancer risk. We found a dose-dependent association between antibiotics exposure up to 15 years in the past and risk of prostate cancer. However, the lack of temporal trends and the absence of class specific effects suggest a noncausal relationship.

Chances of finding an HLA-matched sibling: The Saudi experience.

Hematopoietic cell transplantation (HCT) remains the fundamental procedure to treat many diseases. Its success depends greatly on the degree of HLA matching between donor and recipient. Although the number of successful HCT procedures carried out worldwide increases every year, many patients remain unable to receive this treatment because of the difficulty of finding an HLA-matching donor. In our center, we identified the HLA types for all HCT candidates and their siblings in an attempt to determine the chance of finding a full HLA-matching sibling. Overall, 60% of patients had a chance of finding an HLA-matching sibling. The chance of finding a matching sibling was 43% in patients aged birth to 5 years, compared with 68% in those aged 20+ years. In our Saudi population, patients in need of HCT have a greater chance of finding an HLA-matching sibling than is reported in most Western countries. This is mainly because of the larger number of siblings in most Saudi families. Younger children requiring HCT have a lesser chance of finding an HLA-matching sibling. Our data demonstrate that even in a country with relatively large families, it is still essential to consider alternative donor strategies, such as adult unrelated donors, unrelated umbilical cord blood units, and haploidentical donors.

Hormone therapy for endometriosis and surgical menopause.

BACKGROUND: Endometriosis is characterized by the presence of ectopic endometrial tissue that might lead to many distressing and debilitating symptoms. Despite available studies supporting standard hormone therapy for women with endometriosis and post-surgical menopause, there is still a concern that estrogens may induce a recurrence of the disease and its symptoms. OBJECTIVES: This review aimed to look at pain and disease recurrence in women with endometriosis who used hormone therapy for post-surgical menopause. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialized Register (March 2008), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1966 to March 2008), EMBASE (1980 to March 2008), and references lists of articles. Relevant journals and conference proceedings were handsearched. SELECTION CRITERIA: Randomized controlled trials studying hormone therapy for women with endometriosis in post-surgical menopause. DATA COLLECTION AND ANALYSIS: Review authors assessed the eligibility of trials and their quality. MAIN RESULTS: Two studies fulfilled our inclusion criteria. One trial compared the nonstop transdermal application of 17beta-estradiol (0.05 mg/day) combined with cyclic medroxy progesterone acetate (10 mg per day) for 12 days per month in women with a conserved uterus with nonstop tibolone (2.5 mg/day). The second trial used sequential administration of estrogens and progesterone with two 22 cm(2) patches applied weekly to produce a controlled release of 0.05 mg/day. Micronized progesterone was administered orally (200 mg/day) for 14 days with a 16-day interval free of treatment. Pain and dyspareunia The first trial reported recurrence of pain in the estrogen and progesterone arm in 4/10 of women compared with 1/11 in the tibilone arm. In the latter, 4/115 women reported recurrence of pain in the treatment group compared with 0/57 patients in the no-treatment arm. Neither finding was statistically different.Confirmed recurrence or exacerbation of endometriosis This outcome was not reported in the first trial. The second found that 2/115 of the treatment group developed recurrence of endometriosis with no recurrence reported in the no-treatment group. This was not statistically significant. No woman was re-operated on in the no-treatment group compared with 2/115 in the treatment group. AUTHORS' CONCLUSIONS: Hormone replacement therapy for women with endometriosis in post-surgical menopause could result in pain and disease recurrence. However, the evidence in the literature is not strong enough to suggest depriving severely symptomatic patients from this treatment. There is a need for more randomised controlled studies.