Safety and Efficacy of Convalescent Plasma for Severe COVID-19: Interim Report of a Multicenter Phase II Study from Saudi Arabia.

OBJECTIVE: To present the interim findings from a national study investigating the safety and efficacy of convalescent plasma (CP) containing detectable IgG antibodies as a treatment strategy for severe coronavirus disease 2019 (COVID-19). TRIAL DESIGN AND PARTICIPANTS: An open label, two-arm, phase-II clinical trial conducted across 22 hospitals from Saudi Arabia. The intervention group included 40 adults (aged ≥18 years) with confirmed severe COVID-19 and the control group included 124 patients matched using propensity score for age, gender, intubation status, and history of diabetes and/or hypertension. Intervention group included those (a) with severe symptoms (dyspnea; respiratory rate, ≥30/min; SpO2, ≤93%, PaO2/FiO2 ratio, <300; and/or lung infiltrates >50% within 24-48 h), (b) requiring intensive care unit (ICU) care or (c) experiencing life-threatening conditions. The control group included confirmed severe COVID-19 patients of similar characteristics who did not consent for CP infusion or were not able to receive CP due to its nonavailability. INTERVENTIONS: The intervention group participants were infused 300 ml (200-400 ml/treatment dose) CP at least once, and if required, daily for up to 5 sessions, along with receiving the best standard of care. The control group only received the best standard of care. OUTCOMES: The primary endpoints were safety and ICU length of stay (LOS). The secondary endpoints included 30-day mortality, days on mechanical ventilation and days to clinical recovery. RESULTS: CP transfusion did not result in any adverse effects. There was no difference in the ICU LOS (median 8 days in both groups). The mortality risk was lower in the CP group: 13% absolute risk reduction (P = 0.147), hazard ratio (95% confidence interval): 0.554 (0.299-1.027; P = 0.061) by log-rank test. There was no significant difference in the days on mechanical ventilation and days to clinical recovery. CONCLUSION: CP containing detectable antibodies is a safe strategy and may result in a decrease in mortality in patients with severe COVID-19. The results of the completed trial with a larger study sample would provide more clarity if this difference in mortality is significant. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04347681; Saudi Clinical Trials Registry No.: 20041102.

Unusual presentations, management and outcomes of gastric stromal tumors: a single-center case series.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal tract. This study explores the safety of laparoscopy and the long-term oncological outcome in gastroesophageal GIST treatment. METHODS: A prospectively maintained single-institution database was examined. The variables collected were patient demographics and comorbidities, surgical access (laparoscopic/open), type of surgery, length of stay, and complications. RESULTS: A total of 69 patients underwent GIST resection between January 2011 and June 2018, of whom 56.5% were male; the median age was 68 years (interquartile range 60-76). The majority of patients (78.3%, n=54/69) had a laparoscopic resection. Median length of stay was 6 days in the laparoscopic group and 9 days in the open group (P=0.003). Most patients had wedge excision (n=57/69, 82.6%), while 12 patients (17.4%) required a gastrectomy (one a Merendino type). All patients had an R0 resection and 1 patient (1.4%) had a recurrence, despite having a low-risk grade original tumor with negative margins. Patients in the open group had a significantly higher proportion of patients with a high-risk tumor (50%) compared to the laparoscopic group (3.7%, P=0.001). The mean survival was 92.7 months (95% confidence interval 86.3-99.2). Survival was better in the laparoscopic group (100.4 months) compared with the open group (55.1 months, P<0.001). CONCLUSION: Laparoscopic gastric GIST resection is an oncologically safe alternative to open surgery and is associated with a shorter hospital stay with no difference in complication rates or recurrence rates.

Safety and Efficacy of Convalescent Plasma to Treat Severe COVID-19: Protocol for the Saudi Collaborative Multicenter Phase II Study.

BACKGROUND: The COVID-19 pandemic is expected to cause significant morbidity and mortality. The development of an effective vaccine will take several months to become available, and its affordability is unpredictable. Transfusion of convalescent plasma (CP) may provide passive immunity. Based on initial data from China, a group of hematologists, infectious disease specialists, and intensivists drafted this protocol in March 2020. OBJECTIVE: The aim of this study is to test the feasibility, safety, and efficacy of CP in treating patients with COVID-19 across Saudi Arabia. METHODS: Eligible patients with COVID-19 will be recruited for CP infusion according to the inclusion criteria. As COVID-19 has proven to be a moving target as far as its management is concerned, we will use current definitions according to the Ministry of Health (MOH) guidelines for diagnosis, treatment, and recovery. All CP recipients will receive supportive management including all available recommended therapies according to the available MOH guidelines. Eligible CP donors will be patients with COVID-19 who have fully recovered from their disease according to MOH recovery criteria as detailed in the inclusion criteria. CP donors have to qualify as blood donors according to MOH regulations except for the history of COVID-19 in the recent past. We will also test the CP donors for the presence of SARS-CoV-2 antibodies by a rapid test, and aliquots will be archived for future antibody titration. Due to the perceived benefit of CP, randomization was not considered. However, we will compare the outcome of the cohort treated with CP with those who did not receive CP due to a lack of consent or lack of availability. In this national collaborative study, there is a likelihood of not finding exactly matched control group patients. Hence, we plan to perform a propensity score matching of the CP recipients with the comparator group patients for the major characteristics. We plan to collect demographic, clinical, and laboratory characteristics of both groups and compare the outcomes. A total sample size of 575 patients, 115 CP recipients and 460 matched controls (1:4 ratio), will be sufficient to detect a clinically important hospital stay and 30-day mortality difference between the two groups with 80% power and a 5% level of significance. RESULTS: At present, patient recruitment is still ongoing, and the interim analysis of the first 40 patients will be shared soon. CONCLUSIONS: In this paper, we present a protocol for a national collaborative multicenter phase II study in Saudi Arabia for assessing the feasibility, safety, and potential efficacy of CP in treating patients with severe COVID-19. We plan to publish an interim report of the first 40 CP recipients and their matched comparators soon. TRIAL REGISTRATION: ClinicalTrials.gov NCT04347681; https://clinicaltrials.gov/ct2/show/NCT04347681. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/23543.

Gut barrier dysfunction in critically ill surgical patients with abdominal compartment syndrome.

OBJECTIVES: This study investigated the effects of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on gut barrier function in critically ill surgical patients. METHODS: A prospective observational cohort study on patients with severe acute pancreatitis or abdominal sepsis admitted to an intensive care or high-dependency unit. Intra-abdominal pressure (IAP) and plasma levels of immunoglobulin G (IgG) and IgM antiendotoxin core antibodies (EndoCAb) and procalcitonin (ProCT) were measured serially. RESULTS: Among 32 recruited patients, 24 (75%) and 8 patients (25%) developed IAH and ACS, respectively. The state of ACS was associated with significant reductions in plasma IgG EndoCAb (P = 0.015) and IgM EndoCAb (P = 0.016) and higher concentrations of plasma ProCT (P = 0.056) compared with absence of ACS. Resolution of IAH and ACS was associated with significant recovery of plasma IgG EndoCAb (P = 0.003 and P = 0.009, respectively) and IgM EndoCAb (P = 0.002 and P = 0.003, respectively) and reduction in plasma ProCT concentration (P = 0.049 and P = 0.019, respectively). Negative correlations were observed between IAP and plasma IgG EndoCAb (P = 0.003) and IgM EndoCAb (P = 0.002). CONCLUSIONS: Intra-abdominal hypertension and ACS are associated with significantly higher endotoxin exposure and ProCT concentrations, suggestive of gut barrier dysfunction. Resolution of IAH and ACS is associated with evidence for recovery of gut barrier function.

Clinical relevance of intra-abdominal hypertension in patients with severe acute pancreatitis.

OBJECTIVES: Intra-abdominal hypertension (IAH) contributes to organ failure in patients with abdominal trauma and sepsis and leads to the development of abdominal compartment syndrome (ACS). This study aims to investigate the clinical significance of IAH in patients with severe acute pancreatitis (SAP). METHODS: Patients admitted to intensive care with SAP underwent daily measurement of intra-abdominal pressure (IAP), recording of the clinical data, and calculation of 4 organ dysfunction scores. RESULTS: Among 18 patients with SAP, 11 (61%) developed IAH (median, 20 mm Hg), whereas 10 (56%) developed ACS. The IAP correlated significantly with the 4 organ dysfunction scores; the scores were significantly higher when IAH existed than when it did not. The admission IAP correlated significantly with the duration of intensive care stay. Patients who developed IAH/ACS had significantly higher organ failure score and greater mortality compared with those who did not. Laparotomy and drainage reduced the IAP by a median of -11 mm Hg and relieved the IAH/ACS in all patients. CONCLUSIONS: Intra-abdominal hypertension and ACS are frequent findings in patients with SAP and are associated with deterioration in organ function. Intra-abdominal pressure correlates with the severity of organ failure, and a high admission IAP is associated with prolonged intensive care stay.

Factors predictive of frank intrabiliary rupture in patients with hepatic hydatid cysts.

BACKGROUND/AIMS: Frank intrabiliary rupture (IBR) is a serious complication that occurs in 3-17% of patients. The aim of this study was to identify independent predictors of frank IBR of hepatic hydatid cysts (HHC). METHODOLOGY: Some 741 patients with HHC underwent surgery for HHC between 1965 and 2000. Patient and cyst characteristics were subjected to univariate and multivariate analysis to identify independent predictors of frank IBR. RESULTS: Frank IBR was associated with significantly older age (median, 41 vs. 37 years,p =0.025), more male subjects (40% vs. 32%, p = 0.024), longer duration of symptoms (16 vs. 6 months, p < 0.001), larger cysts (median, 12 vs. 9cm, p < 0.001) and higher incidence of solitary (86% vs. 62%, p < 0.001), multivesicular (89% vs. 39%, p < 0.001), left lobar (38% vs. 13%, p < 0.001) and infected cysts (78% vs. 24%, p < 0.001). Multivariate analysis identified cyst size (> or =10 cm), cyst infection, multivesicular content, solitary cysts and location in the left lobe of liver as well as long duration of symptoms as independent predictors of frank IBR. CONCLUSIONS: Patients with large (> or =10 cm), multivesicular, solitary, left lobar or infected HHC as well as those with prolonged history are at increased risk of frank IBR and should be offered early surgery.

Closed blunt-trocar 5 mm-port for primary cannulation in laparoscopic surgery: A safe technique.

Primary cannulation of the peritoneal cavity is a critical part of laparoscopic surgery. The aim of this study was to evaluate the safety and applicability of a direct blunt-port primary cannulation. The peritoneal cavity was accessed by direct trocar-port insertion at sites other than the umbilicus and avoiding abdominal scars. A 5-mm port with a smooth blunt tip conical trocar was employed using a closed technique. The closed blunt trocar-port technique for primary cannulation of the peritoneal cavity was applied in 503 of 524 patients (96%) who underwent laparoscopic surgery between 2002 and 2005. Some 199 patients (38%) had abdominal scars of previous surgery. There were no major complications, but minor complications occurred in 3 patients (0.6%). No bowel or retroperitoneal vascular injuries were encountered. The closed introduction of a blunt-tipped 5-mm port, conical-trocar is a simple technique for primary cannulation in laparoscopic surgery that allows safe and rapid access to the peritoneal.

Laparoscopic gastric and biliary bypass: a single-center cohort prospective study.

PURPOSE: Relief of gastric outlet and distal biliary obstruction may be accomplished by open surgery or by minimally invasive techniques including endoscopic and laparoscopic approaches. We examined the feasibility and safety of laparoscopic gastric and biliary bypass in all patients with malignant and benign disease requiring surgical relief of obstructive symptoms. MATERIALS AND METHODS: Patients with benign duodenal stricture or inoperable malignancy underwent therapeutic laparoscopic bypass surgery. Prophylactic gastric or biliary bypass was added in selected patients with nonmetastatic malignancy. RESULTS: Twenty-eight patients (17 of them female) with a median age of 67 years (range, 26-81 years) underwent 29 laparoscopic bypass procedures for malignant (n = 23) or benign (n = 6) disease. One patient who underwent a Roux-en-Y gastrojejunostomy for non-steroidal anti-inflammatory drug induced ulcer disease developed stenosis of the stoma that required laparoscopic refashioning 2 months later, accounting for the 29th procedure reported herein in 28 patients. Surgery included the construction of a single gastric (n = 16) or biliary (n = 5) bypass or a double bypass (n = 8), and an additional prophylactic bypass in 5 of 23 cancer patients (21.8%). All procedures were completed laparoscopically. The median operative time was 90 minutes (range, 60-153 minutes) and mean postoperative hospital stay was 4 days (range, 3-6 days). Complications developed following 4 procedures (13.8%) and 1 patient died (3.4%). No complications occurred in patients with prophylactic bypass. One patient required laparoscopic revision of the gastroenterostomy 2 months postoperatively, for benign disease. No recurrence of obstructive symptoms was observed in cancer patients during follow-up. CONCLUSION: Laparoscopic bypass surgery for distal biliary and gastric obstruction in patients with benign or malignant disease results in low morbidity and mortality and short postoperative hospital stay. The addition of prophylactic bypass in patients with nonmetastatic unresectable malignancy appears safe and effective.

Clinical laboratory assessment of acute pancreatitis.

BACKGROUND: Several biochemical markers in blood and urine have been investigated to establish their clinical application in patients with acute pancreatitis (AP). The relevant studies are reviewed and critically appraised. METHODS: Medline and the World Wide Web were searched and the relevant literature was classified under the following categories: (1) diagnosis of AP and (2) prediction of: a) disease severity, b) pancreatic necrosis and its secondary infection, c) organ failure and death, and d) disease etiology. RESULTS AND CONCLUSIONS: Serum lipase is a more reliable diagnostic marker of AP than serum amylase. Urinary strip tests for trypsinogen activation peptide (TAP) and trypsinogen-2 provide a reliable early diagnosis of AP. Useful predictors of severity may include serum procalcitonin and urinary TAP and trypsinogen-2 on admission, serum interleukins-6 and -8 and polymorphonuclear elastase at 24 h, and serum C-reactive protein (CRP) at 48 h. Other markers such as amyloid A and carboxypeptidase B activation peptide (CAPAP) need further investigation. Biochemical prediction of pancreatic necrosis requires 72 h to reach reliability and is impractical. However, the daily monitoring of serum procalcitonin provides a non-invasive detection of infected necrosis; the promising role of phospholipase A(2) in this regard requires further investigation. Early transient hypertransaminasemia reliably predicts biliary etiology, while serum carbohydrate-deficient transferrin and trypsin may predict an alcoholic etiology.

Epidemiology of antibody to hepatitis B core antigen screening among blood donors in Eastern Saudi Arabia. Need to replace the test by HBV DNA testing.

OBJECTIVE: Prevention of the residual risk of transfusion transmitted hepatitis B virus (HBV) infection is mostly relied on serological screening of blood donors for antibody to hepatitis B core antigen (HBc), to detect donors in window period of HBV infection. This study was carried out to determine the prevalence of anti-HBc antibody among blood donors and its impact on rejection of collected blood units. METHODS: Blood bank records of all the blood donors who donated blood at blood bank of King Fahad Hospital, Al-Hofuf, Kingdom of Saudi Arabia, during the period of 2000 to 2003 were reviewed. All the collected blood units were screened for hepatitis B surface antigen (HBsAg), anti-HBc, hepatitis C virus (HCV), human immunodeficiency virus (HIV) 1 and 2, HIV p24, human T-cell lymphotropic virus (HTLV) I/II, venereal disease research laboratory (VDRL) and malaria. All the HBsAg negative with anti-HBc positive units were checked for anti-HBsAg antibodies. RESULTS: Of 26,606 blood donors screened, 514 (1.9%) were HBsAg positive, 853 (3.2%) were isolated anti-HBc positive and 2687 (10.1%) were both anti-HBc and anti-HBsAg positive. The blood units, which were anti-HBc and anti-HBsAg positive, were utilized and the isolated anti-HBc positive blood units were rejected. There was a significant (odds ratio of 1.653, 95% confidence interval 1.298-2.105, p<0.0001) decline in anti-HBc positivity during the study period. CONCLUSION: Isolated anti-HBc positivity as a marker for window period of HBV infection leads to high rejection rate of collected blood units without completely covering the residual risk of HBV transmission by transfusion. Policy for checking the collected blood unit by 3 tests for anti-HBc, anti-HBsAg and HBsAg should be reconsidered in favor of HBV-DNA testing by polymerase chain reaction, to possibly achieve the zero risk goal of transfusion transmitted HBV infection.

Comparison of specimen adequacy in fine-needle aspiration biopsies performed by surgeons and pathologists.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) may yield different results depending on its operator. We compared the proportions of unsatisfactory aspirates obtained by pathologists vs. surgeons. METHODS: In a retrospective review, all FNAB reports and slides performed between March 2002 and February 2003 were grouped by organ/site and according to whether they were done by a pathologist or a surgeon. The proportions of unsatisfactory aspirates for pathologists and surgeons were compared. RESULTS: Of 692 FNABs, 390 were performed by pathologists at the FNAC clinic and the remainder by surgeons. Overall, 15.5% of aspirates obtained were unsatisfactory (n=107). Of aspirates obtained by surgeons, 29.5% were unsatisfactory, compared to 4.6 % of those obtained by pathologists (P<0.001). Pathologists had significantly lower proportions of unsatisfactory aspirates in all sites. A 33% reduction in the number of lymph node excisional biopsies has been reported subsequent to establishment of the FNAC clinic. CONCLUSIONS: The advantages of a pathologist performing FNAB are that a rapid evaluation can be rendered regarding specimen adequacy and the need for repeating the procedure. In addition, pathologists can direct the distribution of aspirated material for other tests such as culture study, flow cytometry and electron microscopy, as indicated by preliminary evaluation of the smears. These factors significantly lower the proportions of unsatisfactory specimens and improve the diagnostic accuracy of FNAB technique.

Fine-needle aspiration biopsy diagnosis of intrathoracic extramedullary hematopoiesis presenting as a posterior mediastinal tumor in a patient with sickle-cell disease: Case report.

Extramedullary hematopoiesis (EMH) is a rare cause of an intrathoracic mass. Fine-needle aspiration biopsy (FNAB) has been only occasionally documented as a useful tool in diagnosing EMH tumor. We report a case of posterior mediastinal extramedullary hematopoietic mass in an 80-yr-old man with sickle-cell anemia. The mass was revealed incidentally on chest X-ray. The definitive diagnosis of this mass lesion was achieved by FNAB. The cytologic smears showed hematopoietic elements with erythroid hyperplasia. A correct cytologic diagnosis can thus help to avoid unnecessary surgical intervention, particularly in an asymptomatic patient.