Liver transplant-associated graft-versus-host disease

BACKGROUND: Graft-versus-host disease (GVHD) is an important, underdiagnosed cause of mortality associated with liver transplantation. We identified 12 cases of GVHD among 1,082 liver transplantations performed in patients at our institution between 1991 and 1998. Patients typically developed fever, skin rash, diarrhea, or pancytopenia within 2 to 6 weeks after their transplant. Treatment generally involved increased immune suppression and hematopoietic cytokines (granulocyte colony stimulating factor, granulocyte monocyte colony stimulating factor); however, all but one patient died, most often from sepsis. Early in its course, GVHD was difficult to distinguish from cytomegalovirus disease or drug reactions. The diagnosis was confirmed by demonstration of substantial donor lymphoid chimerism. METHODS: To identify risk factors for severe GVHD, a retrospective analysis was performed comparing index cases with the rest of the cases in our institutional experience. RESULTS: Closely matched human leukocyte antigen recipients, those older than 65 years, and recipients with donors more than 40 years younger were at higher risk for GVHD. One case occurred in a patient with a congenital immunodeficiency. CONCLUSIONS: Liver transplant-associated GVHD is a progressive and fatal disease. Future approaches should focus on prevention and might include avoidance of closely matched human leukocyte antigen donors, treatment of the donor to reduce the number of lymphocytes, or reduction of immunosuppression in the early posttransplant period.     

Serologic markers of brain injury and cognitive function after cardiopulmonary bypass

OBJECTIVE: To examine the association between biochemical markers of brain injury (MBI) and the inflammatory response in relation to neurocognitive deficiency (NCD) after cardiopulmonary bypass (CPB). SUMMARY BACKGROUND DATA: In cardiac surgery, NCD is a common but underdiagnosed complication with an unclear pathophysiology leading to significant morbidity. Despite extensive investigation, identification of a MBI for clinical use and clarifying the pathophysiology of NCD have not been achieved. METHODS: Forty patients undergoing CABG and/or valve procedures using CPB were administered a validated neurocognitive battery preoperatively and postoperatively at day 4 and 3 months. S-100b, neuron specific enolase (NSE), and tau protein were assayed as MBIs preoperatively and postoperatively at 6 hours and day 4. C-reactive protein (CRP), interleukin (IL)-6, C3a, and total peroxide levels were also quantified from serum. Impact of cardiotomy suction and antifibrinolytics on markers of brain injury was assessed. RESULTS: The incidence of early NCD was 40% (16 of 40). NSE and tau protein at the 6-hour time point were both significantly elevated in the presence of NCD (NCD group) compared with those without NCD (NORM group) (8.69 +/- 0.82 vs. 5.98 +/- 0.61; P = 0.018 and 68.8 vs. 29.2%; P = 0.015; respectively). S-100b increase was not different between the NCD and NORM groups. Cardiotomy suction significantly elevated S-100b levels, whereas NSE and tau were not significantly influenced. Aprotinin did not have an effect on NCD or levels of MBIs. Also, the NCD group had significantly elevated CRP and peroxide levels compared with the NORM group at postoperative day 4 while C3a was significantly elevated at 6 hours. CONCLUSION: NSE and tau are better associated with NCD and less influenced by cardiotomy suction compared with S-100beta. Inflammatory and oxidative stress is associated with NCD post-CPB.     

Ophthalmic Manifestations of Metastatic Breast Cancer

Metastatic breast cancer is the most common primary tumor metastasizing to the ocular structures. An analysis of 30 patients demonstrated a wide spectrum of ophthalmic manifestations including cranial nerve involvement, brain involvement with papilledema, Horner's syndrome, and choroidal and orbital tumors. The mean age of patients presenting with an ophthalmic sign was 54 years and the mean interval from the diagnosis of breast cancer to the development of the ophthalmic sign was 4.9 years. The carcinoembryonic antigen (CEA) was useful in confirming the diagnosis of metastatic disease as it was elevated in 18 of the 22 patients in whom it was measured. The estrogen receptor assay, performed on metastatic tissue removed from the orbit, can indicate the sensitivity of the breast cancer to hormonal therapy.     

Inferior pedicle breast reduction and long nipple-to-inframammary fold distance: How long is safe?

BackgroundFree nipple grafting indications in breast reduction surgery are outdated. Safety of inferior pedicle technique for large resections and long pedicles has not been clearly defined. We evaluated patients who underwent inferior pedicle reduction mammoplasty to define the safety constraints of the inferior pedicle.MethodsA retrospective review of patients who underwent inferior pedicle reduction mammoplasty due to symptomatic macromastia at Mayo Clinic over a six-year period was conducted. Patients with prior breast surgeries were excluded. Demographics, breast measurements, and surgical outcomes were collected. Univariate and multivariate analyses were performed to assess for predictors of necrosis.ResultsOverall, 288 patients (576 breasts) underwent inferior pedicle breast reduction from 2014 to 2019. The mean sternal notch-to-nipple (SNN) distance was 31.5 cm (standard deviation[SD]:4.2; range[r]:16–48), and the mean nipple-to-inframammary fold (N-IMF) distance was 14.8 cm (SD:4.0; r:7.5–27). The mean resection weight was 699.6 g (SD:310.4; r:125–2,385). The median follow-up was 3.9 months (interquartile range[IQR]:2.8–9.0). The overall skin or nipple areolar complex necrosis rate was 2.1%; the overall complication rate was 14.8%. On multivariate analysis, overall necrosis was not found to be associated with the N-IMF distance (adjusted odds ratio[aOR]:1.05, 95%-CI 0.88–1.16). Resection weight was statistically associated with an increased risk of overall necrosis (aOR:1.003, 95%-CI 1.001–1.005), adjusting for N-IMF and SNN distances.ConclusionInferior pedicle breast reduction offers low risk of necrosis and can be safely performed in patients regardless of the N-IMF distance. No association was found between N-IMF distance and overall necrosis in our cohort, including lengths >15 cm. However, large resections could increase the risk of necrosis.     

Management of traumatic popliteal vein injuries

PurposeThe aim of this study was to evaluate different repair methods of popliteal vein injuries, and to assess the relationship between early patency and surgical outcome.MethodsThirty patients with popliteal vein injuries underwent surgical repair procedure at our hospital from March 2000 to April 2010. Patients who were haemodynamically unstable and those with massive bleeding from limb wounds were taken directly to the operating room. Stable patients underwent preoperative colour-flow duplex ultrasonography (CFDU).ResultsOur study group consisted of 26 males and 4 females, ranging in age from 17 to 60 years with a mean age of 25.3 ± 5.9 years. The mechanism of trauma was penetrating in 27 patients and blunt in the remaining 3 patients. Treatment included primary venous repair in 11 cases, end-to-end anastomosis in 8, interposition vein graft in 10, and interposition polytetrafluoroethylene (PTFE) graft in 1. There were 26 patients with associated arterial injury, of which 4 cases had primary repair, 9 had end-to-end anastomosis, 11 had saphenous vein graft interposition, and 2 had PTFE graft interposition. Associated bone fracture was seen in 6 patients. There were no deaths. One patient required a below-knee amputation. Postoperative CFDU revealed thrombosed venous repair in 7 cases without any sequelae.ConclusionPopliteal venous injuries can be repaired with minimal downside and a good early patency rate. Additionally, transient venous patency allows for establishment of venous and lymphatic collateralisation. Alternatively, venous ligation should be considered only in unstable patients who refuse blood transfusion (Jehovah's witnesses). In these victims, adjuvant management may be required such as the use of fasciotomy and anticoagulation treatment.     

Uterine perforation during brachytherapy for cervical cancer: Complications,outcomes, and best practices for forward treatment planning and management

PurposeThe purpose of the study was to determine the incidence of uterine perforations, review the associated complications, and propose guidelines for management of perforations after brachytherapy.Methods and MaterialsA retrospective chart review was conducted for all patients with cervical cancer who received single or multiple high-dose-rate brachytherapy implants between April 2006 and May 2017 at a single academic institution. CT and MRI images were retrospectively evaluated to record incidences of uterine perforation of tandem during brachytherapy. Acute and long-term complications during and after treatment were scored using the Common Terminology Criteria for Adverse Events, Version 4.0, of the National Cancer Institute.ResultsA total of 123 patients were included in the study. Perforations were observed in 22 patients (17.9%) with 31 (6.4%) of the 482 total implants. Of the different categories of adverse events, only the rate of acute infectious complications among those with perforations (n = 3, 13.6%) versus those without perforations (n = 3, 3.0%) was significant (p = 0.040). Two of the three perforated patients with acute infections had mild urinary tract infections, and all resolved without complications or treatment delays. The remaining one patient had a frank perforation of the anterior uterine wall with a subsequent Grade 3 pyometra infection despite administration of prophylactic antibiotics and 1-week treatment delay. This case was eventually resolved with cervical dilation and evacuation of fluid. Long-term complications were not different between the two arms.ConclusionsPatients with cervical cancer with uterine perforations may be able to safely proceed with brachytherapy treatment without delay or need for prophylactic antibiotics in the acute setting. Further validating data would be able to assist in establishing a new standard of care and help prevent unnecessary and harmful breaks during treatment.     

Expanding the Mutational Spectrum of CRLF1 in Crisponi/CISS1 Syndrome

Crisponi syndrome (CS) and cold‐induced sweating syndrome type 1 (CISS1) share clinical characteristics, such as dysmorphic features, muscle contractions, scoliosis, and cold‐induced sweating, with CS patients showing a severe clinical course in infancy involving hyperthermia associated with death in most cases in the first years of life. To date, 24 distinct CRLF1 mutations have been found either in homozygosity or in compound heterozygosity in CS/CISS1 patients, with the highest prevalence in Sardinia, Turkey, and Spain. By reporting 11 novel CRLF1 mutations, here we expand the mutational spectrum of CRLF1 in the CS/CISS1 syndrome to a total of 35 variants and present an overview of the different molecular and clinical features of all of them. To catalog all the 35 mutations, we created a CRLF1 mutations database, based on the Leiden Open (source) Variation Database (LOVD) system ( https://grenada.lumc.nl/LOVD2/mendelian_genes/variants ). Overall, the available functional and clinical data support the fact that both syndromes actually represent manifestations of the same autosomal‐recessive disorder caused by mutations in the CRLF1 gene. Therefore, we propose to rename the two overlapping entities with the broader term of Crisponi/CISS1 syndrome.