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Biomedical subjects

H R Rosen

Publications and source records attributed to H R Rosen.

At least 19 recordsLinked to original sources

Aetiology and surgical management of toxic megacolon.

OBJECTIVE: The purpose of this article is to review the surgical management and outcome of toxic megacolon and to update the aetiology of toxic megacolon. PATIENTS AND METHOD: A retrospective chart review of three academic colorectal surgery units was undertaken. Over a period of 20 years, 70 patients with surgically managed toxic megacolon were identified: 32 men and 38 women, median age 63 years (range, 23-87 years). RESULTS: In 33 (48%) patients the main cause of toxic megacolon was inflammatory bowel disease. Thirty-seven (52%) patients had toxic megacolon of different aetiology. Sixty-three patients underwent colonic resection: 49 (70%) subtotal colectomies and 14 (20%) total colectomies, including 4 (6%) proctocolectomies. Seven (10%) patients had decompression (n=3) or faecal diversion (n=4) only. Forty-four of the resected patients underwent a Hartmann's procedure and an ileostomy; 13 (19%) patients had primary anastomoses, 11 (16%) ileorectal anastomoses (IRA) and 2 (3%) patients had ileal pouch-anal anastomosis (IPAA). Twenty-six (37%) patients subsequently had continuity restored. Total surgical complication rate was 19% (n=13), 8% (n=4) in patients treated with subtotal colectomy, 21% (n=3) in patients treated with total proctocolectomy and 86% (n=6) in patients treated with either decompression or diversion. The total mortality rate was 16% (n=11). CONCLUSIONS: Toxic colitis complicated by toxic megacolon can occur after various diseases of the colon and remains a life-threatening disorder associated with a significant risk of postoperative complications. Subtotal colectomy with ileostomy remains the procedure of choice. Surgical colonic decompression with faecal diversion alone is associated with a high rate of complications.

Adult↗

Patients' expectations of colorectal surgery for cancer.

OBJECTIVE: The primary objectives of surgery for colorectal cancer are to achieve radical resection of the tumour and to ensure a satisfactory quality of life for the patient. But what is satisfactory quality of life for the patients? What do patients desire? The goal of our exploratory investigation was to evaluate prospectively the patient pre-operative expectations as objectively as possible and to analyse results in relation to age, gender and socio-economic status. METHODS: In the period from 1998 to 2001, 167 patients were given a questionnaire consisting of 15 questions prior to surgery. The questionnaire included various aspects that were thought to influence the patient's quality of life. Moreover the patients were given the opportunity to rate the questions they considered most important. RESULTS: The following five points were considered most important by the total group of patients: Complete cure of the disease was rated most important (95%); it was the prime expectation of the patients. This was followed by the avoidance of a stoma (81%), a reliable control of defaecation (52%), normal digestion (44%) and little pain (26%). CONCLUSION: Age, gender and education influence the pre-operative expectations of patients undergoing surgery for colorectal cancer. In addition to the surgical standard, the care of the individual patient must be given due consideration in the treatment strategy.

Adult↗

Improving the safety of laparoscopic cholecystectomy: the routine use of preoperative magnetic resonance cholangiography.

BACKGROUND: The aim of this study was to determine the value of routinely performed preoperative magnetic resonance cholangiography (MRC) in detecting common bile duct (CBD) stones in patients stated to undergo elective laparoscopic cholecystectomy. In addition, we used MRC to investigate possible variants of the cystic duct. METHODS: Magnetic resonance cholangiography was performed preoperatively in 773 patients (311 male and 462 female; median age 55 years, range 16-91) who had no clinical signs of cholestasis prior to undergoing elective laparoscopic cholecystectomy. In cases where the MRC was positive for CBD stones, endoscopic retrograde cholangiopancreatiography (ERCP) was then performed. A total of 532 patients were available for continuous postoperatively follow-up (median 54 months, range 36-85). In 462 patients (247 female, and 215 male), MR images were also reviewed for variants of the cystic duct. RESULTS: In 705 patients (91%), MRC was negative for CBD stones. In 64 patients (9%) MRC was positive. Of these patients, 47 (6%) had CBD stones on ERCP. In 12 patients (2%), MRC was false positive. In five cases (0.6%), ERCP had an inconclusive result postoperative follow-up (532 patients, or 69%) revealed evidence of CBD stones in three patients (10.4%) despite a preoperative negative MRC result. Anatomical variants in the course of the cystic duct and its confluence with the common bile duct were found in 27 of 462 patients (6%). CONCLUSIONS: Magnetic resonance cholangiography proved to be a reliable screening technique in the preoperative evaluation of patients with silent CBD stones. Imaging of the course of the cystic duct is possible in a high percentage of cases. Therefore, MRC can be recommended as a screening technique before laparoscopic cholecystectomy.

Adolescent↗

[Collateral circulation of the left colon: historic considerations and actual clinical significance].

INTRODUCTION: The arterial communication between the superior and inferior mesenteric arteries is important in surgery of the colon and aorta. METHODS: The anastomosis between the median colic artery (ACM) and the superior colic artery (AMS) was studied on 52 cadavers (32 female, 20 male). The length of the artery was measured using a flexible scale, and its diameter was determined at three different locations (origin, middle, end). RESULTS: The median lengths of the arteries were: 6.8 cm (range 3.9-9.7) for ACM, 12.2 cm (range 7-17.4) for ACS, and 23 cm (range 13.6-34.2) for margin artery. The median diameters were: 3.4 mm (range 2.7-4.1) for ACM, 3.1 mm (range 2.1-4.1) for ACS, and 2.7 mm (range 2-3.4) for margin artery. In 9.6% of the cadavers ( n=5), additional anastomoses between the AMS and inferior mesenteric arteries were proven. In 90.4% ( n=47), only margin arteries were found. SUMMARY: The low incidence of an additional communication (Riolan's arch) and possible additional impairment of the blood supply should be taken into account during operation.

Angiography↗

Acute-phase response and immunological markers in morbid obese patients and patients following adjustable gastric banding.

OBJECTIVE: We measured markers of acute-phase response and immunological markers in morbid obese patients and in formerly morbid obese patients after a massive weight loss following adjustable gastric banding (GB). SUBJECTS: A total of 49 morbid obese female patients with a body mass index (BMI) above 40 kg/m(2) were investigated during a study period of 6 months. Of these, 24 patients received a gastric banding (GB) and lost a minimum of 20 kg in 1 y (GB group) and 25 patients maintained their weight (obese group). In sum, 13 normal weight subjects (BMI<24 kg/m(2)) were taken for controls. METHOD: Plasma concentration of the acute-phase proteins, C-reactive protein (CRP), orosomucoid, complement factors C3 and C4 and white blood cell count, lymphocyte subsets and serum immunoglobulins were analyzed. RESULTS: Acute-phase proteins were significantly lower in GB compared to morbid obese patients and remained significantly elevated in GB compared to controls. In addition, leukocytes, polymorphonuclear leukocytes and lymphocytes were significantly lower after GB and reached levels comparable to controls (except PMN). No difference in CD3 counts was observed in the three groups. CD4 increased and CD8 decreased in obese and GB patients when compared to controls whereas no statistical difference was found between obese and GB patients. CONCLUSION: Our results confirm the positive effect of GB followed by a massive weight loss without apparent malnutrition. Subclinical chronical inflammation in morbid obese patients leads to irregularities in leukocyte and lymphocyte subsets. These alterations can be positively influenced by GB.

Acute-Phase Proteins↗

Efficacy and tolerance of a new gentamicin collagen fleece (Septocoll) after surgical treatment of a pilonidal sinus.

OBJECTIVE: Pilonidal sinus is common. It causes substantial loss of working hours. The major disadvantage of open wound treatment is the long time required for healing. Primary wound closure is on the other hand often followed by infection. A controlled, multicentre trial was carried out to evaluate the efficacy of a new gentamicin collagen fleece (Septocoll) combined with primary closure. PATIENTS AND METHODS: One hundred and three patients (88 men, 15 women, median age 30 years) were included. Fifty-one were randomised to gentamicin fleece plus primary closure (Genta Group), and 52 patients to open treatment alone (Open Group). RESULTS: The median interval to wound healing was 17 days in the Genta group and 68 days in the Open group (P = 0.0001, log-rank test). Two patients in Group 1 developed infection within the first two weeks, requiring reopening of the wound, with primary wound healing occurring in 73%. Failure of primary healing (27%) was usually due to seroma or spontaneous dehiscence which subsequently healed. CONCLUSION: The combination of gentamicin collagen fleece (Septocoll) with primary closure resulted in a shorter period to healing than the open technique without unwanted effects.

Adolescent↗

Modern concepts for the treatment of fecal incontinence.

Anal incontinence is estimated to be present in approximately 2% of the total population. However, the incidence of this disorder increases with age, affecting up to 11% of men and 26% of women after the age of 50 years. In general, the causes of long-standing fecal incontinence may be divided into anorectal or congenital malformations, perineal trauma (due to surgery or accident), pudendal nerve lesions with or without muscular injury, and low-motor neuron lesions. Classical surgical treatment includes direct repair of the circumscribed gap in the anal sphincter, the so-called overlapping sphincteroplasty or anal repair. In the short term, this method was shown to be very effective in improving continence. Surgical repair of a diffuse weakness of the pelvic floor by application of the postanal repair method has led to more controversial results. While the short-term results are frequently beneficial, full continence is rarely achieved in the long run, especially in patients with imparied pudendal nerve function. All currently used surgical methods focus on the direct mechanical approach to the pelvic floor muscles and/or the anal sphincter. Therefore, the response to this kind of therapy is limited by the presence of a simultaneously existing neurogenic lesion (pudendal nerve damage), as well as by the magnitude and intensity of muscular injury. These problems have been addressed by the development of new methods that focus on the replacement of large muscular defects (Dynamic Graciloplasty) and the treatment of neurogenic causes of fecal incontinence (Sacral Nerve Stimulation-SNS).

Electric Stimulation Therapy↗

Late mortality after orthotopic liver transplantation.

BACKGROUND: Mortality within the first year after orthotopic liver transplantation (OLTx) is usually due to infection or allograft failure. Late complications leading to death after OLTx have not been extensively evaluated. The aim of this study was to determine the incidence of late mortality and to identify the most common causes and risk factors associated with late mortality after OLTx. METHODS: A total of 479 OLTx were performed in 459 patients (320 males, 139 females; mean age 47 years, range 13 to 69) between September 1991 and April 2000. All patient deaths among liver transplant recipients who survived more than 1 year after transplantation (follow-up mean 3.4 years, median 3, range 1 to 8.6) were reviewed. RESULTS: In all, 122 allografts (24%) were lost in 109 patients during the study period (24%). Seventy-five allografts were lost in 69 patients by 1 year (15%). Forty-seven allografts were lost in 40 patients who survived at least 1 year (9.6%). Actuarial survivals at 2 years, 5 years, and 9 years were 95%, 85%, and 80%, respectively (based on 100% survival at 1 year). The causes of the late mortality were malignancy (9 patients), disease recurrence (8), late infection (6), renal failure complications (5), cardiovascular complications (4), chronic rejection (3), gastrointestinal hemorrhage (2), medication noncompliance (1), and unknown (2). CONCLUSIONS: Malignancy and disease recurrence are the major causes of late mortality among adult OLTx recipients. Pharmacologic immunosuppression is associated with many of the causes of late mortality. Advances in immunosuppression with less toxicity may improve long-term survival after OLTx.

Adolescent↗

Improvement of perineal wound healing by local administration of gentamicin-impregnated collagen fleeces after abdominoperineal excision of rectal cancer.

BACKGROUND: Despite significant advancements in rectal surgery, poor perineal wound healing after abdominoperineal resection (APR) of the anorectum continues to be a potential complication of the procedure. The aim of this prospective randomized multicenter study was to investigate the efficacy of a new mode of local antibiotic administration. PATIENTS AND METHODS: Ninety-seven patients who had to undergo APR for low rectal carcinoma either received sacral drainage plus primary wound closure (control group, n = 48) or the same treatment and supplementary application of three resorbable gentamicin-impregnated collagen fleeces (Septocoll; Merck Biomaterial GmbH, Darmstadt, Germany; Genta group, 49). The following target criteria were investigated: bacteriologic efficacy with respect to the eradication of Enterobacteriaceae, Staphylococcus, and Pseudomonas organisms, and clinical efficacy with respect to perineal wound healing. RESULTS: The Genta group showed a marked reduction in the investigated pathogens from the secretion obtained by sacral drainage on days 1 and 3, as well as high gentamicin concentrations (day 1, median 126.2 microg/mL; day 3, median 97.6 microg/mL). In total, bacteriologic efficacy amounted to 83.7% in the Genta group (41 of 49 patients) versus 60.4% (29 of 48 patients) in controls (P = 0.013). In concurrence with these bacteriologic results, the postoperative infection rate was significantly higher in controls: 10 patients (20.83%) in the control group versus 3 (6.1%) in the Genta group developed perineal or sacral infection (P <0.05). Postoperative complications in the recruited patients revealed no indication of gentamicin-induced adverse reactions. CONCLUSIONS: The results of the study show that the specified dose of 3 Septocoll fleeces in patients with APR is liable to significantly eliminate enterobacteria, staphylococci, and pseudomonads. The clinical course is improved as a result of the bactericidal effect exerted by the gentamicin fleece. The use of Septocoll reduced the incidence of postoperative perineal and sacral infections. Local antibiotic carriers seem to be of great advantage in poorly perfused areas such as the sacral cavity or anatomically problematic regions as the rima ani. In locally contaminated or infected areas, local antibiotic carriers achieve greater concentrations of the active substance than those achieved with systemic antibiotics, even if the latter are administered by the parenteral route.

Absorbable Implants↗

Sacral nerve stimulation as a treatment for fecal incontinence.

BACKGROUND & AIMS: Sacral nerve stimulation is a proven therapeutic option for the treatment of some forms of urinary incontinence. Very recently, preliminary reports have given evidence for its efficacy in fecal incontinence (FI) too. METHODS: Since November 1998, 20 patients have been treated for severe FI. The cause of FI was mainly neurologic (n = 15), and was idiopathic in 5 patients. After temporary (subchronic) external stimulation over a period of 10-14 days, patients whose continence status improved underwent implantation of a permanent quadripolar lead and a subcutaneously implanted pulse generator. RESULTS: Acute (needle) testing revealed a positive pelvic floor response in 16 patients who underwent subsequent permanent implantation. The median number of incontinence episodes decreased from 6 episodes (3-15/21 days) to 2 (0-5/21 days). The time period of retention of a volume of saline causing an urge until definitive defecation was 2 minutes (range, 0-5 minutes) preoperatively and increased to 7.5 minutes (2-15 minutes) postoperatively. Results of preoperative and postoperative (3 months) anal manometry showed a statistically significant increase in maximal resting and squeeze pressures. CONCLUSIONS: Sacral nerve stimulation seems to be a new and promising modality for patients with certain types of FI in whom conventional treatment options have failed to achieve an improvement.

Adolescent↗

Treatment of progressive hepatitis C recurrence after liver transplantation with combination interferon plus ribavirin.

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is common, although the majority of cases are mild. A subset of transplant recipients develops progressive allograft injury, including cirrhosis and allograft failure. Minimal data are available on the safety and efficacy of antiviral treatment in this group of patients. The aim of this study is to review our experience in the treatment of moderate to severe HCV recurrence with combination interferon-alpha2b and ribavirin (IFN/RIB). Between October 1993 and October 1999, a total of 197 patients underwent OLT for HCV-related liver failure. This study describes 12 transplant recipients with moderate to severe recurrence treated with IFN/RIB. All patients met at least 1 of the following inclusion criteria: (1) moderate to severe inflammation (grade III to IV) on allograft biopsy, (2) bridging fibrosis on allograft biopsy, or (3) severe cholestasis attributable solely to HCV recurrence. Two patients had undergone re-OLT for allograft cirrhosis secondary to HCV recurrence and now had evidence of progressive HCV in their second allografts. Appropriate dose reductions of both IFN and RIB, as well as initiation of granulocyte colony-stimulating factor (G-CSF), for marked leukopenia were recorded. IFN/RIB therapy was started 60 to 647 days post-OLT, and duration of therapy ranged from 39 to 515 days. Seven patients were administered G-CSF to successfully treat leukopenia. Six of the 12 patients (50%) became HCV RNA negative by polymerase chain reaction. One of these 6 patients (no. 1) was HCV RNA negative at 6 months but chose to discontinue therapy because of intolerable side effects, experienced a relapse, and was HCV RNA positive at 12 months. Two of the remaining 5 patients were HCV RNA negative at 2 and 9 months off therapy. For the entire group, there was a statistically significant decrease in serum biochemical indices assessed at initiation of therapy and 1, 3, and 6 months into therapy. Most patients required dose reductions of both IFN and RIB. Five patients died; 3 patients died of liver-related complications that included severe intrahepatic biliary cholestasis, severe HCV recurrence, and chronic rejection with profound cholestasis. In the subset of HCV-positive liver transplant recipients with moderate to severe recurrence, combination IFN/RIB therapy resulted in complete virological response (serum RNA negative) in 6 of 12 patients ( approximately 50%). However, only 1 of 12 patients (8.3%) had sustained virological clearance after cessation of IFN/RIB therapy. Dose reductions of both IFN and RIB were required in most patients. The use of G-CSF (sometimes preemptively) allowed correction of leukopenia and full-dose antiviral therapy. Multicenter trials using combination therapy to identify factors predictive of response are needed in the subset of patients with progressive allograft injury.

Adult↗

T-cell clones derived by CD3 stimulation from hepatitis C virus explanted liver tissue are not representative of dominant clones present in vivo.

Liver tissue from hepatitis C virus (HCV)-related end-stage disease contains T-cell infiltrates. The goal of this study is to determine whether CD4 T-cell clones established in vitro using an antigen-independent technique from explanted liver tissue (n = 3) are representative of dominant clones present in vivo. T-cell receptor (TCR) use by intrahepatic CD4 T cells was assessed by spectratype analysis. Clones were established from single CD4 T cells by culturing in vitro with anti-CD3 and interleukin-2 (n > 25 per patient). TCR genes expressed by each clone were identified by sequencing. When identical clones were isolated, the original spectratype was analyzed further to determine whether the clone was a dominant T-cell expansion in vivo. Evidence for clonal expansions was found in all patients by spectratyping. T cells expressing the same TCRBV genes used for spectratyping were cloned in vitro. Duplicate clones expressing the same TCR genes were observed in 2 patients. Confirmation that clones established in vitro matched those present in vivo was obtained for 2 clones. Many dominant clones identified by spectratyping did not proliferate in vitro. Although spectratyping suggested the widespread accumulation of clonal expansions in HCV-related end-stage liver disease, clones established in vitro using anti-CD3 were poorly representative of dominant clones present in vivo. Although cloning with anti-CD3 has the advantage of generating T-cell clones not biased a priori toward a specific antigen, modified cloning strategies will need to be developed to expand those clones that appear dominant in end-stage organs.

Antibodies, Monoclonal↗

Hepatitis B and C in the liver transplant recipient: current understanding and treatment.

1. Liver disease related to chronic viral hepatitis is the leading indication for orthotopic liver transplantation (OLT) worldwide. 2. The natural history of hepatitis B virus infection has been dramatically modified, and outcome has improved substantially in the last decade with the use of hepatitis B immunoglobulin and lamivudine. 3. Hepatitis C virus (HCV) recurrence, defined by histological injury, is almost universal, and a subset of patients (20% to 30%) develops allograft cirrhosis by the fifth year post-OLT. 4. Unfortunately, antiviral therapy for hepatitis C post-OLT, even when initiated preemptively before the development of histological recurrence in the first few weeks post-OLT, has failed to alter the natural history of HCV disease recurrence. 5. HCV-related allograft cirrhosis is associated with a high rate of decompensation and mortality.

Drug Therapy, Combination↗

Hemispheric dominance for emotions, empathy and social behaviour: evidence from right and left handers with frontotemporal dementia.

Although evidence from primates suggests an important role for the anterior temporal cortex in social behaviour, human research has to date concentrated almost solely on the orbitofrontal cortex and amygdala. By describing four cases of the temporal variant of frontotemporal dementia we show how this degenerative condition provides an excellent model for investigating the role of the anterior temporal lobe, especially the right, in emotions, empathy and social behaviour. Assessments of semantic memory, processing of emotional facial expression and emotional prosody were made, empathy was measured, and facial expressions of emotion were coded. Of the two right handers described, one subject with predominantly left temporal lobe atrophy had severe semantic impairment but normal performance on all emotional tasks. In contrast, the subject with right temporal lobe atrophy showed severely impaired recognition of emotion from faces and voices that was not due to semantic or perceptual difficulties. Empathy was lost, interpersonal skills were severely affected and facial expression of emotion was characterized by a fixed expression that was unresponsive to situations. Additionally, two left handers with right temporal lobe atrophy are described. One demonstrated the same pattern of hemispheric lateralization as the right handers and had emotional impairment. The other left hander showed the opposite pattern of deficits, suggesting a novel presentation of anomalous dominance with reversed hemispheric specialization of semantic memory and emotional processing.

Aged↗

Standards for anal sphincter replacement.

PURPOSE: Anal sphincter replacement offers a new treatment option for patients with severe refractory fecal incontinence or for those who require abdominoperineal resection for localized malignancy. The purpose of this study was to review the current status of anal sphincter replacement, formulate a consensus statement regarding its current use, and outline suggestions for future development. METHODS: Four areas of interests were selected: indications for sphincter replacement, continence scoring and quality of life, choice of therapy, and dissemination of new technology. A questionnaire regarding these issues was developed and circulated to working party members; its results served as the basis for this consensus document. RESULTS: Both electrically stimulated skeletal muscle neosphincter and artificial anal sphincter are options for patients with end-stage fecal incontinence. Electrically stimulated skeletal muscle neosphincter is also appropriate for reconstruction after surgical excision of the anorectum in selected cases. Avoidance of complications requires strict attention to sterile technique, prophylactic antibiotics, and deep venous thrombus prophylaxis. A standardized scoring system is proposed that evaluates both continence and evacuation. Quality of life is a critical endpoint for assessing sphincter replacement, and use of The American Society of Colon and Rectal Surgeons incontinence-specific quality-of-life instrument is recommended. As the efficacy of sphincter replacement becomes proven, dissemination of the technique should occur in a controlled manner to ensure adequate surgeon training, minimization of complications, and optimization of results. CONCLUSIONS: Sphincter replacement by electrically stimulated skeletal muscle neosphincter and artificial anal sphincter provide a continent option for patients with end-stage fecal incontinence and those requiring abdominoperineal resection. The guidelines offered in this document are intended to facilitate the controlled and safe development and acceptance of these new techniques.

Anal Canal↗

Association of fungal infection and increased mortality in liver transplant recipients.

BACKGROUND: Invasive fungal infection is associated with increased morbidity and mortality following orthotopic liver transplantation (OLTx). Understanding the risk factors associated with fungal infection may facilitate identification of high-risk patients and guide appropriate initiation of antifungal therapy. OBJECTIVES: The aim of this study was to determine the incidence of fungal infections, identify the most common fungal pathogens, and determine the risk factors associated with fungal infections and mortality in OLTx recipients. METHODS: Medical records from 96 consecutive OLTx in 90 American veterans (88 males, 2 females; mean age 48 years, range 32 to 67) performed from January 1994 to December 1997 were retrospectively reviewed for fungal infection in the first 120 days after transplantation. Infection was defined by positive cultures from either blood, urine (<105 CFU/mL), cerebrospinal or peritoneal fluid, and/or deep tissue specimens. Superficial fungal infection and asymptomatic colonization were excluded from study. All patients received cyclosporine, azathioprine, and prednisone as maintenance immunosuppressive therapy. Fungal prophylaxis consisted of oral clotrimazole (10 mg) troches, five times per day during the study period. RESULTS: Thirty-five patients (38%) had documented infection with one or more fungal pathogens, including Candida albicans (25 of 35; 71%), C torulopsis (7 of 35; 20%), C tropicalis (2 of 35; 6%), non-C albicans (2 of 35; 6%), Aspergillus fumigatus (4 of 35; 11%), and Cryptococcus neoformans (1 of 35; 3%). The crude survival for cases with or without fungal infection was 68% and 87%, respectively (P <0.0001). The median intensive care unit stay and overall duration of hospitalization were significantly longer for patients with fungal infection (P <0.01). The mean time interval from transplantation to the development of fungal infection was 15 days (range 4 to 77) with a mean survival time from fungal infection to death of 21 days (range 3 to 64). Fungal infections occurred significantly more often in patients with renal insufficiency (serum creatinine >2.5 mg/dL), biliary/vascular complications, and retransplantation. CONCLUSIONS: Fungal infections were associated with increased morbidity and mortality following OLTx, with Candida albicans being the most common pathogen. Treatment strategies involving antifungal prophylaxis for high-risk patients and earlier initiation of antifungal therapy in cases of presumed infection are warranted.

Adult↗