Inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C (rs11706052) and 12-month evolution of the graft function in renal transplant recipients on mycophenolate-based immunosuppression.

Variant allele at the inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C has been associated with increased enzyme activity and reduced susceptibility to mycophenolic acid (MPA) in vitro. It has been suggested associated with an increased risk of acute rejection in renal transplant recipients on MPA-based immunosuppression, but not unambiguously. We assessed one-year evolution of the estimated glomerular filtration rate (eGFR) in transplanted variant allele carriers and wild-type subjects, while controlling for a number of demographic, pharmacogenetic, (co)morbidity, and treatment baseline and time-varying covariates. The eGFR slopes to day 28 (GMR = 1.01, 95% CI 0.93-1.09), and between days 28 and 365 (GMR = 1.01, 95% CI 0.99-1.02) were practically identical in 52 variant carriers and 202 wild-type controls. The estimates (95%CIs) remained within the limits of ±20% difference even after adjustment for a strong hypothetical effect of unmeasured confounders. Polymorphism IMPDH2 3757T>C does not affect the renal graft function over the 1st year after transplantation.

Robotic-assisted radical prostatectomy: a multicenter experience with the Senhance Surgical System.

PURPOSE: Robotic-assisted surgery for radical prostatectomy is becoming a standard treatment, and respective implementations are expanding. The Senhance Surgical System is a robotic system with existing but limited data on radical prostatectomy, including a lack of multicenter study experiences. The TRUST study aims to fill this gap and explores observations for radical prostatectomy with the Senhance Surgical System. METHODS: Between August 2019 and November 2022, 375 patients met inclusion criteria from two European sites. Patients' surgical procedure times, data on conversion, malfunction, adverse events, and pain scores were registered and evaluated. Outcomes were calculated for both sides, combined as a total and compared between the initial (1st-150th case) and later (> 150th case) period. RESULTS: The median operating time was 190 min (IQR: 167.5-215.0) and the median docking time was 3 min (IQR: 2.0-5.0). Eighteen cases (4.8%) were converted to standard laparoscopy and two (0.5%) to open. Two perioperative (0.5%) and eleven postoperative adverse events (2.9%) occurred, mostly (83.3%) categorized as mild. Pain scores were reduced from an average of 3.4 (± 1.4) on the postoperative day to 0.9 (± 0.7) at discharge. Compared to our previous data and based on a comparison between our initial and later period, operating time seems to plateau. However, docking time, complication, and conversion rates were successfully reduced. CONCLUSION: We demonstrate progressing safety and efficiency for robotic-assisted radical prostatectomy with the Senhance Surgical System.

Histopathological Features of Time-Zero Kidney Biopsy Are Predictive Factors for Posttransplant Anemia.

INTRODUCTION: Posttransplant anemia (PTA) is a common complication of kidney transplantation, associated with reduced graft survival and higher mortality. We aimed to determine the association of PTA with histopathological characteristics of time-zero allograft biopsy and donor clinical characteristics. METHODS: We conducted a retrospective, observational cohort study that included 587 patients who underwent kidney transplantation in our center. Hemoglobin levels were assessed at 6 and 12 months after transplantation, and anemia was defined according to World Health Organization criteria. The kidney allograft time-zero biopsy has been done in all investigated cases. The evaluated histopathological parameters of the kidney allografts included glomerulosclerosis, arteriolar hyalinosis (AH), vascular fibrous intimal thickening (CV), interstitial fibrosis, tubular atrophy, and interstitial fibrosis and tubular atrophy. The Banff Classification of Allograft Pathology criteria were followed to assess the allograft histopathological changes. RESULTS: The prevalence of anemia was 31.3% at 6 months after transplantation and 23.5% at 12 months. There was an association between 20-50% glomerulosclerosis and PTA in both time points, independently from estimated glomerular filtration rate. AH and interstitial fibrosis were identified as independent risk factors for anemia 6 months after transplantation. CONCLUSION: Histopathological features of time-zero kidney biopsy may be predictors of PTA. Among them, our study recognized 20-50% degree of glomerulosclerosis, AH, and CV as the most significant risk factors for PTA.

FLEXIBLE URETERORENOSCOPY AND LASER LITHOTRIPSY IN A PATIENT WITH A STONE IN THE TRANSPLANTED KIDNEY: A CASE REPORT.

We report a case of a 31-year-old patient with obstructive ureterolithiasis in a transplanted kidney, treated endoscopically with flexible ureterorenoscopy and laser lithotripsy. The patient presented with biochemical signs of acute renal failure and ultrasonographically detected hydronephrosis. Emergency nonenhanced computed tomography scan revealed an obstructive 5-mm stone in the ureter of the transplanted kidney with resulting hydronephrosis. The patient received a double J stent to relieve allograft obstruction. Since the stone size was deemed favorable for conservative treatment, the patient was discharged. Two months later, he was readmitted for leucopenia caused by mycophenolate mofetil. After recuperation of his white blood cell count, he was referred to extracorporeal shock wave lithotripsy, but since the stone was radiolucent, an endoscopic procedure was indicated. Retrograde endoscopic flexible ureterorenoscopy with 'dusting' of the stone was successfully performed. One year after the procedure, the patient was stone free and with good allograft function.

SHORT-TERM OUTCOMES OF PERCUTANEOUS RADIOFREQUENCY AND MICROWAVE ABLATION IN THE TREATMENT OF SMALL RENAL MASSES.

Although the gold standard in the management of kidney tumors is surgical treatment, thermal ablation methods are a viable therapeutic option for patients with small (<4 cm) renal masses who are poor surgical candidates. The aim of this study was to compare the technical success, primary efficacy and complication rate of percutaneous radiofrequency and microwave ablation in the treatment of small renal masses. A retrospective analysis of consecutive patients with small renal masses treated with radiofrequency or microwave ablation between December 2017 and January 2022 was conducted. Response to the ablative therapy was assessed on contrast-enhanced computed tomography examination after 3 months. Ablations of 44 kidney lesions were performed in 43 patients. Sixteen lesions were treated with radiofrequency and 28 with microwave ablation. Both methods were associated with high technical success (100%). Primary efficacy rates of radiofrequency and microwave ablation were 81.3% and 89.3%, respectively. Ablation-related complications were noted only in the patients treated with microwave ablation (18.5%), all of them being low grade (Clavien-Dindo 1 and 2). Radiofrequency and microwave ablation exhibited comparable efficacy in the treatment of small renal masses. Microwave ablation was associated with a comparatively higher number of complications.

SACRAL NEUROMODULATION IN TREATING OVERACTIVE BLADDER PATIENTS - FIRST-TIME APPLICATION IN CROATIA.

Sacral neuromodulation (SNM) is a safe, efficacious, and minimally invasive advanced therapy that involves electrical stimulation to sacral nerve root to modulate neural pathway. Indications for SNM include symptoms of overactive bladder (OAB), urinary incontinence, urinary retention, urgency and frequency and, regarding bowel dysfunction, fecal incontinence . In Europe and Canada, indication is also established for chronic constipation. The mechanism of action is still not fully elucidated and complete understanding is yet to be determined. It is proposed that SNM modulates neural circuits in both central and peripheral pathways, thus having an impact on the brain, as well as on the bladder-targeting neuronal activity. Another possible significant effect on irregular bladder activity is through inhibition of the bladder afferent pathways by stimulation of the pudendal nerve. Over the past two decades, with more than 300 000 treated patients, SNM has confirmed its efficacy to relieve refractory OAB symptoms, as well as urinary retention or fecal incontinence. First SNM applications in Croatia were uneventful and we are glad to offer our patients this novel therapy in the future.

LAPAROSCOPIC ADRENAL-SPARING SURGERY CASE SERIES: PARTIAL ADRENALECTOMY AND CYST RESECTION.

The aim is to present our case series documenting indications, laparoscopic technique, surgical and endocrinologic outcomes of laparoscopic partial adrenalectomy. In the period from April 2011 until October 2021, we performed 39 procedures. The patients were divided into three groups: unilateral adrenal gland tumor with a normal contralateral gland (group 1), tumor of the solitary adrenal gland (group 2), and adrenal cysts (group 3). There were 20 patients in group 1, 6 patients in group 2, and 13 patients in group 3. The most common histology in group 1 was adenoma (40%), all tumors in group 2 were renal cell carcinoma metastases, and all cysts in group 3 were benign. There were no major complications (Clavien Dindo grade ≥2) in the whole cohort. All patients in groups 1 and 3 had favorable endocrinologic outcomes, and 50% of group 2 patients required lifelong hydrocortisone replacement therapy. The procedure is safe and feasible with favorable outcomes in the hands of a high volume adrenal surgeon.

OPEN RADICAL CYSTECTOMY: SINGLE CENTER RESULTS AND OUTCOMES IN THE LAST FIVE YEARS.

Radical cystectomy is a therapeutic modality of choice for many patients with muscle-invasive bladder cancer. We conducted a retrospective study of open radical cystectomies performed at a single Center from January 2017 to January 2022. Decision on the urinary diversion type was based on tumor stage, comorbidities, patient age, general condition and preferences. There were 19.5% of female and 80.5% of male patients, median age 67 (range 38-90) years. We performed 96 (44.7%) ureterocutaneostomies (UCS), 67 (31.2%) ileal conduit derivations, and 52 (24.2%) orthotopic neobladder derivations (OND). There were 17 (7.9%) complications after UCS, 7 (3.2%) after incontinent urinary diversion, and 7 (3.2%) after OND. Fifty-five (25.6%) patients developed early complications, of which 31 (14.4%) during the initial hospitalization period, and 24 (11.2%) required re-hospitalization in the 30-day postoperative period. The most common wound-related complication was wound dehiscence, most typically caused by infection. The main reason for readmission was urosepsis. The 30-day mortality rate was 0.9%. Late complications that occurred 30 days after the operation were found in 39 (18.1%) cases. Bladder cancer is a high-mortality disease that requires a multidisciplinary and personalized approach. Further development of multidisciplinary teams, perioperative and postoperative care, and follow-up strategy is needed to improve the oncologic and functional outcomes of this procedure.

MANAGEMENT OF PROSTATE CANCER IN KIDNEY TRANSPLANT RECIPIENTS.

Kidney transplantation is the treatment of choice in eligible patients with end-stage kidney disease. Prostate cancer (PC) is the second most common cancer in men worldwide. The prevalence of chronic kidney disease worldwide is 13.4%. The management of localized PC in these patients is challenging due to immunosuppressive therapy and pelvic graft localization. High graft and recipient survival rates have resulted in higher numbers of these patients in our everyday practice. A retrospective analysis of male patients who had undergone kidney transplantation at our center between 2002 and 2022 and were diagnosed and treated for PC was performed. We analyzed the incidence, treatment methods, and follow-up of PC patients in this population. A total of 1079 male patients were transplanted. PC was diagnosed in 12 patients (8 after and 4 before transplantation). The incidence of PC was 1.11%. Radical prostatectomy was performed in 11 patients, and one patient was treated with radical radiotherapy. Eleven patients had stable graft function; 1 graftectomy was performed, unrelated to PC. Three patients were indicated for salvage radiotherapy, one is in process for prostate-specific membrane antigen positron emission tomography (PSMA PET CT), and 7 patients are in follow-up and without recurrence. Radical prostatectomy is a safe treatment method for localized PC in kidney transplant recipients, which does not impair graft function and survival.

POSTPROSTATECTOMY CONTINENCE AFTER FUNCTIONAL MAGNETIC PELVIC STIMULATION.

Although radical prostatectomy is considered the gold standard for optimal treatment of localized prostate cancer, this radical surgery carries a significant risk of erectile dysfunction and urinary incontinence which can be present as transient or permanent side effects in many patients. We have made significant advances in diagnostic and surgical approach to prostate cancer, using a number of new methods that are becoming increasingly available, resulting in better treatment outcomes. However, we still do not use all the possibilities for the prevention and treatment of these side effects, probably due to their insufficient research, or unclear effectiveness. Functional magnetic stimulation is a method used to treat a large number of diseases, i.e., to alleviate their symptoms and ailments. Its role through pelvic stimulation has been proven in the treatment of incontinence in women, and in our study, we want to determine its role in more detail, primarily in the treatment of urinary incontinence in patients after prostate cancer surgery. In case of positive results, this method may be recommended for wider use in patients with adverse effects of radical prostatectomy.

TRENDS IN SURGICAL MANAGEMENT OF RENAL NEOPLASMS: SINGLE CENTER RESULTS IN THE LAST DECADE.

The majority of renal neoplasms can be treated surgically using open or minimally-invasive approach. Nephron-sparing surgery should be used when possible, regardless to the operative approach. In this retrospective study, we analyzed surgical trends of operative treatment of renal neoplasms in the period from February 2011 until December 2020. There were a total of 1031 procedures, 703 (68.2%) radical nephrectomies (RN) and 328 (31.8%) partial nephrectomies (PN). Laparoscopic approach was used in 211 (20.5%) (111 PN and 100 RN), while open approach was used in 820 (79.5%) (328 PN and 703 RN) cases. There were 12 procedures performed with the use of cardiopulmonary bypass and hypothermic arrest. The median operative time was 161 minutes for open RN and 158 for open PN, 160 for laparoscopic RN, and 162 for laparoscopic PN. The most common pathology was clear cell carcinoma in 693 (67.3%), papillary carcinoma in 115 (11.2%), chromophobe carcinoma in 67 (6.5%), oncocytoma in 46 (4.5%), and angiomyolipoma in 33 (3.2%) patients. Pathologically, pT1 stage was diagnosed in 56.9%, pT2 in 5.8%, pT3 in 22.4% and pT4 in 1.2% of patients. Regional lymphadenectomy was performed in 354 (34.3%) patients, among which lymph nodes were positive in 40 (11.3%) cases. Surgical margins were positive in 27 cases when PN was performed (8.2%). In conclusion, there was an ongoing raising trend in the number of procedures in general, and also in minimally invasive and nephron-sparing surgery in our study.

Hospitalization and death after recovery from acute COVID-19 among renal transplant recipients.

INTRODUCTION: Data on post-COVID-19 in renal transplant recipients (RTR) is scarce. We investigated the rate of hospitalizations, reasons for hospital admission, and mortality rate among RTR who survived acute COVID-19. METHODS: A multi-center retrospective observational cohort study measured hospital admission and death to 180 days after acute SARS-CoV-2 infection in 308 adult patients. RESULTS: The median age was 57 years, 64.9% were male. All patients had at least one comorbidity, and 26.3% had diabetes. Data on post-COVID-19 course was available for 267 patients, and 49 of them (15.9%) required hospital treatment after recovery from the acute infection. The most common indications included pneumonia (24.5%) and renal allograft dysfunction (22.4%), 7 (14.3%) had sepsis and 5 (10.2%) had thrombotic events. A median duration of the hospital stay was 12 days. Six patients (2.2%) died due to multiorgan failure, respiratory insufficiency or urosepsis. The strongest predictor for hospitalization after acute COVID-19 was hospitalization for acute SARS-CoV-2 infection, while better allograft function decreased the probability of hospitalization. CONCLUSION: Delayed consequences of acute COVID-19 are highly prevalent and the health care systems should be prepared to respond to the needs of RTR suffering from post-COVID-19 complications.

Urethral pressure profile before radical prostatectomy as a predictor of early postoperative continence.

OBJECTIVE: Urinary incontinence (UI) is one of the most common complications of radical prostatectomy (RP). Impaired urethral sphincter function is generally considered to be the most important contributing factor for UI; however, the mechanism of onset and recovery of urinary continence has not been fully elucidated. The objective of this research was to evaluate preoperative functional urethral length (FUL) and maximum urethral closure pressure (MUCP) as early continence recovery predictors after open retropubic RP (ORRP). METHODS: The research was conducted on a group of 43 patients with localized prostate cancer (PCa) in the period from July 2019 to May 2021. The urodynamic method of urethral pressure profile (UPP) was used to assess FUL and MUCP, and correlate with the postprostatectomy continence recovery. The severity of UI and bothersome were assessed using fully validated International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF) and number of pads used in 24 h. Patients were interviewed about the use of urinary pads and asked to fill out the ICIQ-UI SF before and 2, 8, 16 and 24 weeks after ORRP. RESULTS: The median value of FUL (mm) and MUCP (cmH2O) was 69 (28-94) and 76 (16-223), respectively. Correlation and linear regression showed a statistically significant negative correlation between preoperative values of FUL and MUCP with ICIQ symptom score and the number of pads used per day at the four observed time intervals (p < 0.05). Such a result showed that patients with higher preoperative FUL and MUCP values were more likely to recover urinary continence earlier. A value of 65 mm for FUL and 80 cmH2 O for MUCP proved to be the cut-off values for continence recovery in 24 weeks after ORRP. CONCLUSION: Preoperatively evaluated FUL and MUCP seem to be valuable prognostic factors for early continence recovery after ORRP. Further investigation on a larger patient cohort is needed to evaluate the role of UPP in the preoperative management of patients with PCa.

Senhance robot-assisted adrenalectomy: a case series.

We present a case series of 12 consecutive robot-assisted adrenalectomies performed from May 2019 to March 2020 by a single surgeon experienced in laparoscopy using the novel Senhance robotic system. Eleven patients had primary aldosteronism due to an adrenal adenoma, diagnosed by means of endocrinological and radiological evaluation, and 1 had a benign adrenal cyst. The robotic adrenalectomy technique is described in detail. The mean procedure time was 165.1 minutes, with robotic docking time of 11.6 minutes and console time of 98.6 minutes. The mean estimated blood loss was 47 mL, and hospital stay duration was 4.5 days. There was 1 Clavien Dindo IIIB complication and 1 patient underwent conversion to laparoscopy. All patients with adenoma had complete biochemical remission after surgery. In conclusion, the Senhance robotic system is a safe and feasible platform for benign adrenal surgery in high-volume centers.

LAPAROSCOPIC RADICAL PROSTATECTOMY: SINGLE CENTER CASE SERIES.

Laparoscopic radical prostatectomy (LRP) is traditionally characterized as a technically difficult procedure with a long learning curve but it is successfully performed worldwide. The aim of this paper was to assess the initial learning curve and clinical outcomes for LRP in our center. We performed a retrospective study including 63 LRP cases, in the course of 22 months, performed by 2 urologists, with no previous LRP experience. All patients were previously assessed by a multidisciplinary team and were selected on the basis of low and intermediate risk disease attributes according to the classification of prostate cancer risk groups of the European Association of Urology. The main outcomes of follow-up are procedure duration, estimated blood loss, complications, positive surgical margins, biochemical relapse and urinary continence. The median follow-up was 19.6 months. The median procedure duration was 196.8 minutes and median blood loss 257.1 mL. Significant decrease in both outcomes was observed when comparing first and last cases in the series. There were 5 (7.9%) Clavien Dindo grade II complications. Undetectable prostate specific antigen (PSA) was observed in 59 (93.6%) patients, and fifty-five patients (87.3%) were continent. Following a methodical learning approach, LRP can be safely mastered with favorable outcomes.

PELVIC REHABILITATION FOR URINARY INCONTINENCE AFTER RADICAL PROSTATECTOMY.

Radical prostatectomy (RP) performed by open, laparoscopic, or robotic approach is considered the gold standard for localized prostate cancer (PCa). However, it carries the risk of postprostatectomy urinary incontinence (UI) and erectile dysfunction (ED) which significantly reduce patients' satisfaction with surgery and quality of life (QoL), therefore it is important to decrease the possibility or severity of these complications to a minimum. There are several preoperative prognostic factors such as urethral length and closing pressure obtained by magnetic resonance imaging and profilometry, as well as several variations in the surgical approach such as preservation of the neurovascular bundle (NVB) and puboprostatic ligaments, sparing or reconstruction of bladder neck, Retzius-sparing approach, and meticulous surgical dissection, used to predict or prevent unwanted side effects of RP. In addition, there are postoperative methods that can help reduce complications. In this review, we will present the role of pelvic rehabilitation with an emphasis on pelvic floor muscle training (PFMT) in reducing consequences of radical surgery.

SCROTAL THERMOGRAPHY IN THE EVALUATION OF SURGICAL OUTCOME AFTER VARICOCELE REPAIR: A CASE REPORT.

Scrotal thermography is a diagnostic method for varicocele. In short, there are five diagnostic thermographic criteria for varicocele, i.e., pattern of scrotal thermographic image indicative of varicocele, temperature at pampiniform plexus ≥34 C°, temperature difference between left and right pampiniform plexus ≥0.5 C°, enhancement of image during Valsalva maneuver, and temperature at pampiniform plexus ≥ temperature at ipsilateral thigh. Three or more positive signs are indicative of varicocele. The aim of this report is to present the use of digital thermography as a diagnostic method to evaluate the outcome of varicocele repair. We present a case of a student diagnosed with varicocele grade III, and assessed preoperatively and followed up postoperatively by scrotal thermography. According to thermographic indicators, our patient was positive for varicocele diagnosis before surgical treatment. Three months after varicocele repair, the patient did not show positive thermographic indicators of varicocele while physical examination and color Doppler ultrasound were equivocal. This case report suggests that infrared digital thermography of scrotum could be very valuable for monitoring patients in the period after surgery for varicocele, however, it should be confirmed in a larger number of patients.

ANESTHESIA FOR ROBOT-ASSISTED RADICAL PROSTATECTOMY - A CHALLENGE FOR ANAESTHESIOLOGIST.

Mininimally invasive surgery has become one of the most popular ones over the last few decades due to many benefits. The advantages are minimal surgical incision, reduced blood loss, reduced postoperative pain, faster postoperative recovery, shorter hospital stay, lower morbidity and better outcomes compared to open surgery. The most common robotic procedures in urology are radical prostatectomies. In UHC Zagreb, since November 2019 until now, there have been more than 180 robotic assisted radical prostatectomies (RALP) using Senhance robotic system performed. As a procedure with many possible complications, it represents a challenge for anaesthesiologist. Some of the problems the anaesthesiologists have to face are related to limited patient access, possible difficulties connected with positioning, pneumoperitoneum, subcutaneous emphysema, possible airway oedema. Pneumoperitoneum has impact on almost every system: cardiovascular, renal, respiratory, gastrointestinal and other. Detailed understanding of physiological changes of RALP, with intraoperative impact on nearly every body system is ultimate. Careful preoperative evaluation and intraoperative conduction minimize the risk of complications, and help patients to reach full recovery in a very short time. Excellent outcomes are the result of individualized approach to the patient and good communication between team members.

SENHANCE ROBOTIC RADICAL PROSTATECTOMY.

Since its introduction 20 years ago, robotic radical prostatectomy has become a standard of care in the treatment of localized prostate cancer in many Centers. Until recently, they have all been performed by the only available robotic platform. Senhance is a novel robotic platform that was approved for clinical use. The term Senhance was used to systematically search PubMed and Scopus databases for relevant articles that were afterward filtered for appropriate designs and data reports. There were two reports that met all of the criteria and were included in the review. Both studies were designed as prospective case series with a total of 234 patients where the data including operative data and oncological outcomes were reported. The average operative time ranged between 180 and 195 min, with estimated blood loss between 250 and 300 mL. There was 3 Clavien - Dindo grade III, and 1 Clavien - DIndo grade IV complication reported. One of the studies compared it with laparoscopy, but no significant difference in operative time and blood loss was found. Both studies concluded that the Senhance is a feasible and safe robotic platform for radical prostatectomy.

Histopathologic findings on indication renal allograft biopsies after recovery from acute COVID-19.

Current knowledge on histopathological changes occurring after COVID-19 in transplanted kidneys is limited. Herein, we present renal allograft pathology findings in patients recovered from COVID-19. Six patients underwent indication biopsy, and one required allograft nephrectomy after acute COVID-19. Demographic data, clinical characteristics, and laboratory findings were recorded. The histopathological analysis included light microscopy, immunostaining, and electron microscopy. Five patients were hospitalized for acute COVID-19, and all were diagnosed with imaging-confirmed pneumonia, one requiring mechanical ventilation, and two requiring dialysis. Two patients had mild form. Histopathologic examination of renal allograft specimens revealed collapsing, perihilar, tip-lesion and secondary FSGS in one patient each. One patient had borderline acute cellular rejection, and two had chronic antibody-mediated rejection. Histopathologic changes of glomerular tufts were accompanied by acute tubular injury in four patients. None of our patients had signs of viral inclusions in kidney cells. One patient died and one remained dialysis-dependent after the good initial response to treatment. Patients with collapsing and perihilar FSGS had further progression of their chronic allograft nephropathy still without need for dialysis. In conclusion, diverse kidney pathology may be found in SARS-CoV-2-infected renal transplant patients. It seems that viral infection may affect the immune system with triggering of glomerular diseases, while the acute tubular injury is of multifactorial etiology. Direct viral effect is less likely.