The neutrophil/lymphocyte ratio as a prognostic factor in COVID-19 patients: a case-control study.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has been identified in China as responsible for viral pneumonia, now called COVID-19 (Coronavirus Disease 2019). Patients infected can develop common symptoms like cough and sore throat, and, in severe cases, acute respiratory syndrome and even death. To optimize the available resources, it is necessary to identify in advance the subjects that will develop a more serious illness, therefore requiring intensive care.The neutrophil / lymphocyte ratio (NLR) parameter, resulting from the blood count, could be a significant marker for the diagnosis and management of risk stratification. PATIENTS AND METHODS: A retrospective, single-center case-control observational study was conducted. The differential cell count of leukocytes, the NLR and the clinical course of patients hospitalized in intensive care with COVID-19 were analyzed, comparing them with other patients (COVID-19 and non-COVID-19) and healthy individuals selected among workers of the Teaching Hospital Policlinico Umberto I in Rome. RESULTS: 370 patients (145 cases and 225 controls) were included in the case-control study, 211 males (57%) and 159 females (43%). The average age of the population was 63 years (SD 16.35). In the group of cases, out of 145 patients, 57 deaths and 88 survivors were recorded, with a lethality rate of 39.3%. The group of cases has an NLR of 7.83 (SD = 8.07), a much higher value than the control group where an NLR of 2.58 was recorded (SD = 1.93) (p <0.001). The Neutrophils / Lymphocytes ratio may prove to be a diagnostic factor for COVID-19, an NLR> 3.68 revealed an OR 10.84 (95% CI = 6.47 - 18.13) (p <0.005). CONCLUSIONS: The value of NLR considered together with the age variable allows a risk stratification and allows the development of diagnostic and treatment protocols for patients affected by COVID-19. A high neutrophil to lymphocyte ratio suggests worse survival. Risk stratification and management help alleviate the shortage of medical resources and reduce the mortality of critically ill patients.

Non-adherence to Mediterranean diet and synergy with lifestyle habits in the occurrence of breast cancer: a case-control study in Italy.

OBJECTIVE: The aim of this study was to assess the synergistic effect of non-adherence to the Mediterranean Diet (MD) and lifestyle habits on the occurrence of breast cancer (BC). PATIENTS AND METHODS: A case-control study was carried out from September 2018 to February 2019 at the Teaching Hospital "Umberto I" in Rome. A Food Frequency Questionnaire was used for assessing the level of adherence to MD, the IPAQ Questionnaire to measure physical activity, and AUDIT-C to estimate alcohol consumption. The possible interaction between risk factors was tested using the synergism index. RESULTS: A total of 94 cases and 88 controls were enrolled (median age 55.8 for cases and 57.9 for controls). The MD Score over 6 was associated with low odds of having breast cancer (OR = 0.29; 95% CI: 0.12-0.69). There is a clear indication for the additivity and synergism between non-adherence to MD and many risk factors on the occurrence of BC: current smoker (S = 2.02; 95% CI 0.62-8.07), physical inactivity (S = 2.14; 95% CI 0.71 2-8.28) and alcohol consumption (S = 3.02; 95% CI 0.91-12.95). CONCLUSIONS: Primary prevention of BC can benefit from intervention targeting nutritional and lifestyle factors that act synergistically.

Addressing morbid obesity as a barrier to renal transplantation with laparoscopic sleeve gastrectomy.

Morbid obesity is a barrier to renal transplantation and is inadequately addressed by medical therapy. We present results of a prospective evaluation of laparoscopic sleeve gastrectomy (LSG) for patients failing to achieve significant weight loss with medical therapy. Over a 25-month period, 52 obese renal transplant candidates meeting NIH guidelines for metabolic surgery underwent LSG. Mean age was 50.0 ± 10.0 years with an average preoperative BMI of 43.0 ± 5.4 kg/m(2) (range 35.8-67.7 kg/m(2)). Follow-up after LSG was 220 ± 152 days (range 26-733 days) with last BMI of 36.3 ± 5.3 kg/m(2) (range 29.2-49.8 kg/m(2)) with 29 (55.8%) patients achieving goal BMI of <35 kg/m(2) at 92 ± 92 days (range 13-420 days). The mean percentage of excess weight loss (%EWL) was 32.1 ± 17.6% (range 6.7-93.8%). A segmented regression model was used to compare medical therapy versus LSG. This revealed a statistically significant increase in the BMI reduction rate (0.3 kg/m(2)/month versus 1.1 kg/m(2)/month, p < 0.0001). Patients also experienced a 40.9% decrease in anti-hypertensive medications (p < 0.001) and a 49.7% decrease in total daily insulin dose (p < 0.001). LSG is a safe and effective means for addressing obesity in kidney transplant candidates in the context of a multidisciplinary approach.

Effects of heavy metals on ultrastructure and Hsp70 induction in Lemna minor L. exposed to water along the Sarno River, Italy.

The effects of freshwater pollution in the highly contaminated river Sarno (Campania, Southern Italy) have been evaluated using bags containing the aquatic plant Lemna minor (Lemnacee, Arales), in order to determine morpho-physiological modifications as a response to pollutants. The exposition of Lemna bags for 7 days on three different sites along the river path showed alterations in chloroplasts and vacuoles shape and organization. Moreover, some specimens were exposed in vitro at the same heavy metal (HM) concentrations measured in the polluted sites of the river, and compared with data from the bag experiment; to verify the dose and time dependent effects, samples were exposed to HM in vitro at concentrations ranging from 10(-6) to 10(-4)M up to 7 days. Transmission electron microscopy (TEM) observations on in vitro plants confirmed that ultrastructural alterations affected most of plastids and the shape of different subcellular structures, namely vacuoles; in in vitro stressed specimens, Heat Shock Proteins 70 (Hsp70) levels changed, in dependence of changing levels of HM measured in different sites along the river path. Thus L. minor exhibited a possible correlation between the levels of HM pollution and Hsp70 occurrence; interestingly, the data presented showed that copper specifically increased Hsp70 levels at concentrations detected in polluted river waters, whereas cadmium and lead did not; on the other side, the latter represent highly toxic elements when specimens were exposed to higher levels in vitro. The effects of specific elements in vitro are compared to those observed in bags exposed along the river path; thus results are examined in order to propose L. minor as an organism able to be utilized to monitor heavy metals pollution; the possibility of using Hsp70s as specific markers of HM pollution is discussed.

Prospective iterative trial of proteasome inhibitor-based desensitization.

A prospective iterative trial of proteasome inhibitor (PI)-based therapy for reducing HLA antibody (Ab) levels was conducted in five phases differing in bortezomib dosing density and plasmapheresis timing. Phases included 1 or 2 bortezomib cycles (1.3 mg/m(2) × 6-8 doses), one rituximab dose and plasmapheresis. HLA Abs were measured by solid phase and flow cytometry (FCM) assays. Immunodominant Ab (iAb) was defined as highest HLA Ab level. Forty-four patients received 52 desensitization courses (7 patients enrolled in multiple phases): Phase 1 (n = 20), Phase 2 (n = 12), Phase 3 (n = 10), Phase 4 (n = 5), Phase 5 (n = 5). iAb reductions were observed in 38 of 44 (86%) patients and persisted up to 10 months. In Phase 1, a 51.5% iAb reduction was observed at 28 days with bortezomib alone. iAb reductions increased with higher bortezomib dosing densities and included class I, II, and public antigens (HLA DRß3, HLA DRß4 and HLA DRß5). FCM median channel shifts decreased in 11/11 (100%) patients by a mean of 103 ± 54 mean channel shifts (log scale). Nineteen out of 44 patients (43.2%) were transplanted with low acute rejection rates (18.8%) and de novo DSA formation (12.5%). In conclusion, PI-based desensitization consistently and durably reduces HLA Ab levels providing an alternative to intravenous immune globulin-based desensitization.

Long-term results after proactive management for locoregional control in patients with colonic cancer at high risk of peritoneal metastases.

PURPOSE: A major problem in treating patients with peritoneal spread from colorectal cancer is that at diagnosis wide peritoneal involvement often precludes all curative attempts. A possible solution is to identify those patients at risk for peritoneal metastases and intervene early to prevent locoregional disease spread before it develops and, thus, to improve outcome. METHODS: We analyzed long-term results from a previous study and compared outcomes in 25 patients with advanced colon cancer considered at high risk for peritoneal spread (pT3/pT4 and mucinous or signet ring cell histology) prospectively included and managed with a proactive surgical approach including target organ resection for peritoneal spread plus hyperthermic intraperitoneal chemotherapy (HIPEC) and in 50 retrospectively well-matched controls who underwent standard surgical resection during the same period and in the same hospital by different surgical teams. RESULTS: At 48 months after the study closed, peritoneal metastases and local recurrence developed significantly less often in proactively managed patients than in controls (4 vs 28%) (p < 0.03). Patients in the proactive group also survived longer than control patients (median overall survival 59.5 vs 52 months). Despite similar morbidity, Kaplan-Meier survival curves disclosed significantly longer disease-free and overall survival in the proactive than in the control group (p < 0.05 and <0.04). CONCLUSIONS: In patients with advanced colon cancer at risk for peritoneal recurrence, the proactive surgical approach plus HIPEC seems to achieve good locoregional control preventing peritoneal spread thus improving outcome without increasing morbidity. These advantages merit investigation in a multicentric randomized trial.

Randomized controlled pilot study of B cell-targeted induction therapy in HLA sensitized kidney transplant recipients.

Optimal induction regimens for patients at high risk for antibody and/or cell-mediated rejection have not been established. This pilot, prospective, randomized study evaluated addition of B cell/plasma cell-targeting agents to T cell-based induction with rabbit antithymocyte globulin (rATG) in high immunologic risk renal transplant recipients. Patients were randomized to induction with rATG, rATG + rituximab, rATG + bortezomib or rATG + rituximab + bortezomib. Inclusion criteria were: (1) current cytotoxic panel reactive antibody (PRA) ≥20% or peak cytotoxic PRA ≥50% or (2) T or B cell positive flow crossmatch with donor-specific antibody (DSA) or (3) historical positive serologic or cytotoxic crossmatch or DSA to donor or (4) prior allograft loss with more than one acute rejection. Median overall follow-up was 496 days: 1-year and overall acute rejection were 25% and 27.5%, and 25% of patients developed de novo DSA within 1 year. One-year and overall patient survival were 97.5% and 92.5%, and 1-year and overall death-censored allograft survival were 97.5% and 95%. Renal allograft function posttransplant was similar among all arms. Eight of nine cases of peripheral neuropathy were mild, whereas one case was moderate and required a narcotic prescription. In conclusion, addition of rituximab and/or bortezomib to rATG induction has an acceptable safety/toxicity profile in a high immunologic risk renal transplant population.

Proteasome inhibition reduces donor-specific antibody levels.

BACKGROUND: Current antibody-mediated rejection (AMR) therapies (intravenous immunoglobulin, apheresis, rituximab, polyclonal antibodies) do not target the primary antibody producing B cells, that is, the plasma cell. We report the preliminary results from the first clinical experience with plasma cell targeted therapy with bortezomib. Bortezomib is approved by the US Food and Drug Administration for the treatment of plasma cell tumors (multiple myeloma). METHODS: Kidney transplant patients with mixed acute cellular rejection (ACR) and AMR episodes (by Banff '97 criteria, update 2005) were treated with bortezomib (1.3 mg/m(2) per dose x 4) at standard labeled doses. Patients were monitored by serial donor specific anti-HLA antibody (DSA) determinations [Luminex/Labscreen beads] and quantified by conversion to fluorescence intensity to molecules of equivalent soluble fluorescence (MESF). RESULTS: Five patients were treated with bortezomib. Each patient also had coexisting ACR. In each case, bortezomib treatment led to prompt ACR and AMR rejection reversal. DSA levels decreased significantly in all patients (except 1 patient who had short follow-up). Observed toxicities from bortezomib included a transient grade III thrombocytopenia (1 patient) and mild-to-moderate nausea, vomiting, and/or diarrhea (3/5 patients). Opportunistic infections were not observed. CONCLUSIONS: Bortezomib therapy provides effective reduction in DSA levels with long-term suppression. These preliminary results indicate that proteasome inhibition provides an effective means for reducing HLA antibody levels in transplant recipients.

Corticosteroid avoidance ameliorates lymphocele formation and wound healing complications associated with sirolimus therapy.

INTRODUCTION: Sirolimus (RAPA) and corticosteroids (CS) both inhibit wound healing. To evaluate the possibility that RAPA and CS have additive effects on wound healing, we evaluated the effects of corticosteroid avoidance (CSAV) on wound healing complications in patients treated with RAPA. METHODS: One hundred nine patients treated with a CSAV regimen (no pretransplantation or posttransplantation CS) were compared with a historical control group (n = 72) that received cyclosporine (CsA), mycophenolate mofetil (MMF), and CS. The CSAV group received low-dose CsA, MMF, RAPA, and thymoglobulin induction. Complications were classified as follows: wound healing complications (WHC) or infectious wound complications (IWC). WHC included lymphocele, hernia, dehiscence, diastasis, and skin edge separation. IWC included wound abscess and empiric antibiotic therapy for wound erythema. RESULTS: The CSAV group was largely CS-free: 11% of patients received CS for rejection, 12% of patients received CS for recurrent disease, and 85% of patients are currently off CS. The CSAV group had a significantly lower incidence of WHC (13.7% vs 28%; P = .03) and lymphoceles (5.5% vs 16%; P = .02) than the control group. There was no difference in the incidence of IWC between the 2 groups. Patients who received CSAV were 18% less likely (P = .57) to develop any type of complication, 41% less likely (P = .20) to develop a WHC, and 71% less likely (P = .018) to develop a lymphocele. CONCLUSIONS: CSAV in a RAPA-based regimen results in a marked reduction in WHC and lymphoceles. Therefore, CSAV provides a promising approach for addressing WHC associated with RAPA therapy.

A prospective, pilot study of early corticosteroid cessation in high-immunologic-risk patients: the Cincinnati experience.

BACKGROUND: The first prospective trial of steroid withdrawal dedicated to high-immunologic-risk patients is reported herein. METHODS: Twenty-five patients were enrolled prospectively in an IRB-approved HIPAA-compliant protocol. Immunosuppression included corticosteroid withdrawal (CSWD) at 7 days, tacrolimus (target trough level 4 to 8 ng/mL), sirolimus (target trough level 8 to 12 ng/mL), and Mycophenolate Mofetil (2 g/d). Induction with daclizumab (2 mg/kg) on posttransplant days (PTD) 0 and 14 was administered to the first 10 patients. The protocol for the next 15 patients was modified because of high acute rejection rates to include received T-cell-depleting antibody induction therapy with thymoglobulin (1.5 mg/kg) on PTDs 0 and 2 followed by daclizumab on Postoperative day (POD) 14. Recipient inclusion criteria included: (1) repeat transplant recipients; or (2) patients with a peak PRA > or =25%. All rejection episodes were diagnosed by biopsy and graded using Banff '97 criteria. RESULTS: Twenty-five patients were enrolled and median follow-up was 402 days. Forty percent of recipients were black, 68% of patients were repeat transplant recipients, 68% received deceased donor kidneys, and 36% had a peak flow PRA >25%. Overall acute rejection, graft survival, and patient survival rates of 40%, 88%, and 96%, respectively, were observed for the duration of the study. Acute rejection occurred in 6 of 10 patients (60%) with daclizumab induction; however, acute rejection rates fell to 27% when thymoglobulin was introduced (P = .1). CONCLUSIONS: This study supports our previous observations in a multivariate analysis of early CSWD patients, wherein polyclonal antibody induction therapy reduced acute rejection. High-immunologic-risk patients may be able to undergo early CSWD with acceptable rates of acute rejection.

Histocompatibility testing predicts acute rejection risk in early corticosteroid withdrawal regimens.

UNLABELLED: Histocompatibility testing has been shown to predict acute rejection risk in steroid-based immunosuppression. However, little evidence exists of its ability to predict acute rejection risk in corticosteroid-free patients, with no evidence in early corticosteroid withdrawal (CSWD) under modern immunosuppression. The purpose of this study was to evaluate the ability of histocompatibility testing to identify patients at high risk for acute rejection after early CSWD. METHODS: One hundred eighty-one patients were entered into six IRB-approved early CSWD regimens. Histocompatibility testing included serologic PRA, flow cytometric PRA testing by Class I and Class II MHC beads, and B cell crossmatching with pronase treatment. All rejection episodes were biopsy proven, and grading was assigned using Banff criteria. Influence of individual tests was examined using Chi square univariate and multivariate logistic regression analysis. RESULTS: Median follow-up was 23.5 months (range 7-48 months). Of 181 patients, 16% were repeat transplant recipients, 36% received deceased donor renal transplants, 48% received living related donor renal transplants, and 16% received living unrelated transplants. Overall patient survival was 97%, and death-censored graft survival was 96.5%. Acute rejection rates in the entire follow-up period were 17.7%. 12.4% in primary transplant recipients and 37% in repeat transplant recipients. Multivariate analysis revealed that HLA AB and DR locus mismatching were associated with increased acute rejection risk. Similarly, serologic PRA analysis predicted acute rejection risk; however, flow cytometry crossmatching did not predict acute rejection risk. The greatest single influence on acute rejection risk appeared to be a flow cytometric B cell crossmatch (7.94-fold increased risk). In conclusion, histocompatibility testing can identify patients at high risk for acute rejection following early CSWD. HLA matching, serologic PRA testing, and flow cytometry-based B cell crossmatching can all be used to predict acute rejection risk.

African American renal transplant recipients benefit from early corticosteroid withdrawal under modern immunosuppression.

African Americans have historically been considered high-risk renal transplant recipients due to increased rejection rates and reduced long-term graft survival. Modern immunosuppression has reduced rejections and improved graft survival in African Americans and may allow successful corticosteroid withdrawal. Outcomes in 56 African Americans were compared to 56 non-African Americans enrolled in early withdrawal protocols. Results are reported as African American versus non-African American. Acute rejection at 1 year was 23% and 18% (P = NS), while patient and graft survival was 96% versus 98% and 91% versus 91% (P = NS), respectively. In conclusion, early withdrawal in African Americans is associated with acceptable rejection rates and excellent patient and graft survival, indicating that the risks and benefits of early withdrawal are similar between African Americans and non-African Americans. Additional followup is needed to determine long-term renal function, graft survival, and cardiovascular risk in African Americans with early steroid withdrawal.

Early steroid withdrawal does not increase risk for recurrent focal segmental glomerulosclerosis.

UNLABELLED: Experience with early corticosteroid withdrawal (CSWD) in renal transplant recipients with focal segmental glomerulosclerosis (FSGS) has not been previously reported. Since corticosteroids are used to treat primary FSGS, concern exists as to whether early CSWD regimens will be associated with an increased risk of FSGS recurrence posttransplant. The purpose of the present study was to evaluate the results of early CSWD in FSGS recipients and compare these results to a historic control group of FSGS patients who underwent renal transplantation under corticosteroid-based immunosuppression. METHODS: Forty-three patients with FSGS underwent renal transplantation with early CSWD. Results in these patients were compared to FSGS patients that underwent renal transplantation with chronic corticosteroid therapy. All rejection episodes were biopsy proven with grading by Banff criteria. Statistical analyses included Student's t test and chi square tests. RESULTS: Results in 43 patients with a median follow-up of 569 days were analyzed and compared to control patients. There was no significant difference in recurrent FSGS, time to recurrence, or graft loss. CONCLUSION: CSWD does not increase risk for recurrence of FSGS. These observations indicate that ECSW can be achieved in FSGS patients, thereby affording them the benefits of steroid elimination.

Outcomes of patients with rejection post-polyomavirus nephropathy.

INTRODUCTION: We sought to determine the effects of rejection in renal transplant recipients with polyomavirus nephropathy (PVN). METHODS: SCr, biopsy findings, BKV serum and urine loads (Taqman PCR), and BKV antibody titers (HA inhibition assay) were analyzed by two-sample median tests and z tests in 11 patients with median follow-up of 7.3 (2.0 to 31.5) months post-PVN. All patients underwent immunosuppression reduction (ISR) as PVN treatment. RESULTS: Post-PVN, 3 (27%) patients had five rejection episodes, with 80% being mild. Median time to rejection was 18 (2 to 60) weeks. One hundred percent of patients who experienced post-PVN rejection also experienced rejection pre-PVN. Rejection episode treatments consisted of: none in one, increased tacrolimus in two, IVIG in one, IVIG and increased tacrolimus in one. Median viral loads in patients with post-PVN rejection versus those without rejection were not different in serum (2.01 x 10(4) vs 9.00 x 10(4) BKV copies/mL; P = .22) or urine (5.37 x 10(5) vs 8.93 x 10(6) BKV copies/mL; P = .28). Median BKV antibody titers were slightly lower (16384 vs 32768 HA units; P = .02) and median SCr values were significantly higher (2.7 vs 1.9 mg/dL, P = .0003) in patients who had experienced post-PVN rejection. Graft losses occurred in one rejection-free patient (chronic allograft nephropathy) and in one patient who experienced multiple acute rejection episodes, humoral rejection, and worsening PVN. CONCLUSIONS: Patients who experience rejection prior to PVN are at high risk of developing rejection post-ISR and post-PVN; however, low graft loss rates may still be achieved.

Gastrointestinal surgical emergencies in patients treated for hemathological malignancies.

BACKGROUND: Upper and lower gastrointestinal symptoms are major and serious complications in patients who undergo chemotherapy for hematological malignancies. Their most frequent causes are acute intestinal graft-versus-host disease (GVHD) after bone marrow transplant, infections, toxicity or preexisting gastrointestinal diseases. Mortality can reach 30-60% of cases. PATIENTS AND METHODS: We report 15 cases operated on for abdominal emergencies: 3 severe gastrointestinal bleeding and 12 acute abdomen. RESULTS: We performed 10 bowel resections, one cholecystectomy, one splenectomy, two laparotomy with pancreatic debridement and peritoneal lavage, and one suture of perforated peptic ulcer. Operative mortality was 33.3% (5/15). Deaths have been reported only in the group of patients with acute abdomen. In all cases death was correlated to generalized sepsis related to immunosuppression. CONCLUSIONS: We believe that an aggressive approach, consisting of close monitoring and early laparotomy combined with vigorous supportive therapy, should be used when dealing with suspected gastrointestinal complications in patients with hematological malignancies.

Results of emergency surgery in patients with Moschowitz's disease refractory to hematological treatment: is splenectomy always advisable?

BACKGROUND: Patients with thrombotic thrombocytopenic purpura (TTP), Moschowitz's disease, run a high risk of perioperative bleeding and need intensive hematologic support. In some patients, TTP is associated with cancer but the surgical role in these patients is still unclear. To illustrate the surgical problems and outcome we present the case histories of three patients with TTP observed in our emergency department. MATERIALS AND METHODS: Two patients had TTP secondary to cancer and one patient with primary TTP (no evidence of neoplasia) had emergency operation for gastric hemorrhage, occlusion and TTP unresponsive to plasmapheresis. RESULTS: The first two patients who had not radical resection of cancer and no splenectomy, died for TTP complications. The third patient who underwent emergency splenectomy, had an uneventful postoperative course and TTP completely regressed. CONCLUSIONS: These case reports suggest that patients with TTP should be screened to rule out cancer. In patients with acute cancer-related complications emergency surgery should aim to resect the cancer. An associated splenectomy may increase the effectiveness of postoperative hematologic therapy.

Systematic radical gastrectomy and D2 lymphadenectomy in primary gastric B cell lymphoma: impact on diagnosis, classification and long term results. A prospective study.

The role of surgery in the treatment of primary gastric lymphoma has been recently re-evaluated. We report the results of a series of 37 operated patients for primary gastric lymphoma (PGL). All patients underwent gastrectomy with D2 lymphadenectony and bilateral liver biopsies. Postoperative histopathological classification was compared to preoperative staging data. No mortality and low morbidity were observed in this series of patients. We found a high incidence of mixed grading of tumors and a relatively high incidence of lymph node metastases in low grade lymphoma. Relying on preoperative biopsies and imaging techniques could lead to preoperative staging inaccuracy and therefore to inappropriate treatment planning. For these reasons we advocate systematic primary surgery in PGL. Surgery could be useful for staging purposes and seems to be curative in stage IE.