A Prospective Randomized Trial of Steroid-Free Maintenance Regimens in Kidney Transplant Recipients—An Interim Analysis

We compared three maintenance immunosuppressive regimens in a rapid discontinuation of prednisone protocol. From March 1, 2001, through December 31, 2003, 239 first and second kidney transplant recipients (166 LD; 73 DD) were randomized. All recipients were treated with Thymoglobulin; all received steroids intraoperatively and for 5 days postoperatively. Randomization was to cyclosporine-mycophenolate mofetil (n = 85); high-level tacrolimus (TAC) (8-12 ng/mL)-low-level sirolimus (SRL) (3-7 ng/mL) (n = 72); or low-level TAC (3-7 ng/mL)-high-level SRL (8-12 ng/mL) (n = 82). We found no difference at 24 months between groups in patient, graft, death-censored graft, or acute rejection-free graft survival, or in kidney function. Wound complications were more common in SRL-treated recipients (p = 0.02); we found no other differences between groups in complication rates. Our data suggest that excellent patient and graft survival and low rejection rates can be obtained using a variety of maintenance protocols without prednisone.     

Use of extended pattern technique for initial prostate biopsy

PURPOSE: An extended prostate biopsy schema has been advocated at initial prostate biopsy to decrease the rate of false-negative cancer cases. However, critics have raised concerns that this may lead to the greater detection of clinically insignificant cancers. We examined the impact of using an extended pattern schema on cancer detection and also on the finding of smaller and clinically insignificant cancer. MATERIALS AND METHODS: Clinical data, including patient age, race, prebiopsy prostate specific antigen (PSA), digital rectal examination, prostate volume, number of needle cores and biopsy findings were abstracted from the medical records of all patients who underwent prostate biopsy in a 5-year period. Extended pattern prostate biopsy was defined as more than 10 cores. Clinically insignificant cancer was defined as a maximal tumor dimension of 1.0 cm or less, Gleason sum 6 or less and organ confined disease at radical prostatectomy. Adjusted regression models were developed to assess the independent effects of using an extended biopsy pattern on the detection of cancer overall and on the detection of clinically insignificant cancer. RESULTS: A total of 740 men with a mean age of 62.6 years were referred for prostate biopsy. Median PSA was 5.7 ng/ml and prostate volume was 39.7 cc. The OR for detecting prostate cancer was 1.55 (95% CI 1.09 to 2.19) for the extended pattern compared with standard biopsy. Of the subset of 136 patients who underwent radical prostatectomy 12.6% had clinically insignificant cancer. However, in contrast to overall cancer detection, extended pattern prostate biopsy was not found to be associated with an increased risk of detecting smaller or clinically insignificant cancer. PSA density was the single parameter found to be independently associated with the detection of clinically insignificant cancer (95% CI 0.20 to 0.98). CONCLUSIONS: Using an extended prostate biopsy pattern involving more than 10 cores increases the likelihood of detecting prostate cancer. A significant association between more needle cores at initial prostate biopsy and finding smaller and clinically insignificant cancer was not apparent.     

Treatment with convalescent plasma in solid organ transplant recipients with COVID-19: Experience at large transplant center in New York City

Solid organ transplant (SOT) recipients may be at higher risk for poor outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Convalescent plasma is an investigational therapy that may benefit immunosuppressed patients by providing passive immunity. Convalescent plasma was administered to hospitalized patients with coronavirus disease-2019 (COVID-19) at an academic transplant center in New York City. Eligible patients were hospitalized and required to have positive nasopharyngeal polymerase chain reaction (PCR) diagnosis of SARS-CoV-2 infection, be at least 18 years old, and have either dyspnea, blood oxygen saturation ≤ 93% on ambient air, respiratory frequency ≥ 30 breaths/min, partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, or lung infiltrates > 50%. Thirteen SOT recipients received convalescent plasma from April 9, 2020, to May 17, 2020. The median time from symptom onset to plasma infusion was 8 days. Eight of 13 patients (62%) had de-escalating oxygenation support by day 7 post-convalescent plasma. Nine (69%) patients were discharged, 1 (7%) patients remain hospitalized, and 3 (23%) patients died. This series supports the need for additional studies on convalescent plasma use in SOT recipients with COVID-19 to better determine efficacy and identify patients who are likely to benefit.     

Computed tomography of the lacrimal drainage system: retrospective study of 107 cases of dacryostenosis.

PURPOSE: To evaluate the role of computed tomography in patients with dacryostenosis. METHODS: One hundred seven cases of dacryostenosis (94 patients) were assessed by thorough clinical and lacrimal history and examination, and lacrimal region computerized tomography (CT). The lacrimal drainage system examination included the state and position of the puncta; Jones testing; lacrimal syringing; and, in the latter half of the study, telescopic nasal endoscopy. The patients were drawn from the hospital outpatients and private office of the operating lacrimal surgeon in this series (I.C.F.). Of the 107 cases, 79 either underwent dacryocystorhinostomy surgery or had this planned. RESULTS: In 14 of the 107 cases (12 patients), preoperative CT led to an alteration of patient management, usually referral to an otolaryngologist for further evaluation or treatment. In addition to the detection of two tumors extrinsic to the sac, conditions such as ethmoiditis, lacrimal sac mucoceles, soft tissue opacity in the nasolacrimal duct, gross nasal polyposis, fungal sinusitis, and a dacryolith were observed by CT. CONCLUSION: Similar to the role of functional endoscopic sinus surgery in otolaryngology, CT imaging will become increasingly important in the assessment of many patients with symptoms of lacrimal drainage obstruction.     

Cervical spinal cord injury--a public catastrophe

Cervical spine cord injuries continue to be a major cause of death and disability for trauma victims. Motor vehicle trauma results in 500 to 650 quadriplegic patients per year. Most of the patients are cared for at Level I trauma centers which may not have a dedicated rehabilitation facility. Long-term rehabilitation, nursing care, and financial support remain difficult areas in the overall management of these injuries. Seventy-one cervical spine fracture patients were admitted to this medical center over a 2-year period. Twenty-two patients had a neurologic injury, 15 quadriplegic patients, and seven with incomplete deficits. Vehicular trauma was the etiology in 14 injuries; gunshot wounds in five; falls in three. Twelve of these 22 patients had associated injuries, including chest and abdominal trauma. Prolonged stays in the intensive care unit were common (avg. = 13.5 days). Bronchoscopy (8/22 patients) and aggressive pulmonary care were constantly needed. Six patients died in the intensive care unit. The average hospital stay of the survivors was 45 days. Three of the 16 surviving patients were ventilator dependent at the time of discharge. Ten patients were discharged to a rehabilitation center, one to a nursing home, and five went home (one on a ventilator). The total hospital charges were $1,250,000. No financial resources were available for five of the 16 surviving patients. Four patients had resources which covered less than 50% of the total charges. Average hospital charges for survivors were $50,370. Maximum reimbursement using all outlier days under DRG 5 would be $12,385. The financial support of initial hospitalization, rehabilitation, and nursing care for these quadriplegic patients is a serious national health care issue.     

Antibody immunotherapy of gram-negative bacterial sepsis in an immunosuppressed animal model

Leukopenic, immunosuppressed recipients of solid organ allografts are at high risk for gram-negative bacterial sepsis, and mortality remains unacceptably high (greater than 30%). The purpose of this study was to determine whether murine monoclonal antibody (MAb) directed against lipopolysaccharide (LPS, endotoxin) would reduce lethality caused by a septic insult in immunosuppressed mice, and to determine if a specific antibody class would prove more efficacious in this setting. Two MAbs (3-H9, IgG3; 7-B5, IgM) were selected that reacted by ELISA, immunodot blot, and Western blot analysis against the O antigen polysaccharide portion of Escherichia coli 0111:B4 LPS. The 3-H9 MAb, 7B-5 MAb, or sterile saline was administered i.v. to normal or neutropenic Swiss-Webster mice immediately prior to an E coli 0111:B4 bacterial (i.v. or i.p. plus hemoglobin) or LPS (i.v.) challenge. In normal mice, administration of 3-H9 MAb or 7-B5 MAb i.v. immediately prior to a bacterial or endotoxin challenge resulted in a significant increase in the LD50. Neutropenia lowered the LD50 by nearly one log10 in both the bacteremia and peritonitis models. Both MAbs provided similar protection, raising the LD50 one log10 in neutropenic mice. Thus neutropenic animals receiving either MAb had a mortality nearly identical to that of normal animals receiving saline. No significant difference between the protective capacity of these MAbs was noted in any of the three models. These studies demonstrate that MAbs directed against LPS exert protection during gram-negative bacterial sepsis in either normal or neutropenic animals. In addition, the particular IgG and IgM MAbs examined provided similar protective capacity. Antibody directed against LPS may provide an additive form of therapy that may serve to decrease lethality during clinical gram-negative sepsis in immunosuppressed patients.     

Fibrinogen and Fibrin Clot Structure in Diabetes

Diabetes is associated with an increased risk of developing cardiovascular disease, which is not fully accounted for by the accumulation of classic cardiovascular risk factors in patients. Recent evidence has demonstrated fibrinogen to be a powerful independent risk marker for cardiovascular disease in the general population, and it is also likely to contribute toward the increased atherosclerotic risk in diabetes. The etiology of hyperfibrinogenemia in diabetes is likely to be multifactorial, and at present the mechanisms involved have not been clarified. However, insulin, insulin resistance and inflammation are likely to be involved, especially in type 2 diabetes. The influence of diabetes in determining an individual's atherothrombotic risk is likely to extend beyond that of elevated fibrinogen levels, and may also act via changes in the structure and function of the fibrin clot that forms. Further research is needed to determine the mechanisms underlying these changes, which may lead to development of future interventions to reduce the excessive vascular risk associated with this disease.