Treatment options in first-line metastatic renal carcinoma: A meta-analysis of 2556 patients treated with immune checkpoint inhibitors-based combinations in randomised controlled trials.

BACKGROUND & AIMS: The average five-year survival of metastatic renal cell carcinoma (mRCC) is 71%. However, there is significant variability in patient prognosis. Immune checkpoint inhibitors (ICIs) have been introduced into the treatment landscape of mRCC. This meta-analysis aimed to estimate progression-free and overall survival probabilities and identify possible outcome predictors of mRCC patients treated with ICI combination as first-line treatment. METHODS: Studies comparing the combination of ICI combinations versus standard of therapy for first-line treatment of advanced renal-cell carcinoma were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through September 2023. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using the DerSimonian and Laird methods. RESULTS: Six studies met the inclusion criteria. Globally, 5121 patients were included in this meta-analysis: 2556 patients treated with immune checkpoint inhibitors and 2565 with sunitinib as control. The ICI combination was associated with improved PFS (hazard ratio (HR) 0.68; 95 % confidence interval (CI), 0.56-0.81, p < 0.0001). Furthermore, ICI combination was also associated with OS improvement (HR 0.85; 95 % CI, 0.78-0.92, p = 0.001). There is no statistical increase in adverse events. CONCLUSIONS: Our findings show that PFS and OS are statistically increased in mRCC with ICI combination treatment by 32% and 15%, respectively.

Artificial Intelligence-suggested Predictive Model of Survival in Patients Treated With Stereotactic Radiotherapy for Early Lung Cancer.

BACKGROUND/AIM: Overall survival (OS)-predictive models to clinically stratify patients with stage I Non-Small Cell Lung Cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT) are still unavailable. The aim of this work was to build a predictive model of OS in this setting. PATIENTS AND METHODS: Clinical variables of patients treated in three Institutions with SBRT for stage I NSCLC were retrospectively collected into a reference cohort A (107 patients) and 2 comparative cohorts B1 (32 patients) and B2 (38 patients). A predictive model was built using Cox regression (CR) and artificial neural networks (ANN) on reference cohort A and then tested on comparative cohorts. RESULTS: Cohort B1 patients were older and with worse chronic obstructive pulmonary disease (COPD) than cohort A. Cohort B2 patients were heavier smokers but had lower Charlson Comorbidity Index (CCI). At CR analysis for cohort A, only ECOG Performance Status 0-1 and absence of previous neoplasms correlated with better OS. The model was enhanced combining ANN and CR findings. The reference cohort was divided into prognostic Group 1 (0-2 score) and Group 2 (3-9 score) to assess model's predictions on OS: grouping was close to statistical significance (p=0.081). One and 2-year OS resulted higher for Group 1, lower for Group 2. In comparative cohorts, the model successfully predicted two groups of patients with divergent OS trends: higher for Group 1 and lower for Group 2. CONCLUSION: The produced model is a relevant tool to clinically stratify SBRT candidates into prognostic groups, even when applied to different cohorts. ANN are a valuable resource, providing useful data to build a prognostic model that deserves to be validated prospectively.

Effectiveness of Radiofrequency Ablation for Treatment of Glossopharyngeal Neuralgia: A Systematic Review of the Current Literature.

BACKGROUND: Glossopharyngeal neuralgia (GPN) is a rare cause of facial pain that has an incidence of less than one per 100,000 people. The excruciating stabbing pain experienced by patients with GPN can be debilitating, leading to difficulties in activities of daily living, such as eating and speaking. As a result, there has been a recent increase in research on the effectiveness of radiofrequency ablation (RFA) for treating GPN. OBJECTIVE: The objective of our study was to evaluate the effectiveness of (RFA for treating GPN while examining its impact on patients' quality of life and assesses for any associated side effects. STUDY DESIGN: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) model was employed to identify articles from 2 comprehensive medical databases. The patient outcomes and numbers from each article were aggregated and calculated in order to determine the percent efficacy of RFA for treating pain associated with GPN. METHODS: In this systematic review, the PRISMA review model was utilized to search through the PubMed and EMBASE databases. A comprehensive literature review was conducted. Of the initial 1,580 articles identified, 18 articles were included for analysis. Studies included in this systematic review encompassed idiopathic cases and secondary causes, such as an elongated styloid process, oropharyngeal cancers, and postsurgical/traumatic pain. RESULTS: Of the 288 patients treated with RFA, 231 experienced relief or complete resolution of pain, yielding an efficacy rate of 80.2%. Most of the patients experienced immediate pain relief after RFA; however, some patients reported numbness, dysphagia, and changes in taste. Our study examines the potential use of RFA as a minimally invasive and effective treatment for GPN. LIMITATIONS: Limitations of our study include the absence of comparisons between different types, modes, and settings of RFA procedures. The use of only 2 medical databases is another limitation. Finally, our systematic review does not include any randomized controlled trials. CONCLUSION: RFA is efficacious in treating GPN with over 80% of patients experiencing postprocedure pain relief. However, further research in the form of clinical and controlled trials is needed to contribute to a better understanding of RFA's long-term outcomes for patients with GPN.

Water quality and health risk assessment of heavy metals in groundwater of Ranbir Singh Pura tehsil of Jammu and Kashmir, India.

Groundwater is one of the important sources available for drinking, agricultural, domestic, and various other purposes in the study area. Study area is having agricultural importance and is famous for Basmati rice production in the world. In order to assess water suitability for irrigation and drinking purposes, 25 sampling sites were selected and water samples were collected from handpumps, borewells and motors from May 2022 to June 2022. Fifteen physico-chemical parameters and water quality index (WQI) was calculated to assess the drinking water suitability. The results obtained then compared with the BIS (2012) and WHO drinking water guidelines. For irrigation water suitability, irrigation water quality index (IWQI) and other indices were calculated. Heavy metal health risk assessment was also evaluated using target hazard quotient (THQ), carcinogenic risks (CR), non-carcinogenic risks, heavy metal pollution index (HPI), etc. Study found 60% of water samples under poor category of WQI. All water samples were found suitable for irrigation purposes according to different indices except for permeability index for which only 32% samples were found suitable. IWQI classifies 52%, 32%, and 12% of water samples under moderate, low, and no restriction category respectively. Groundwater of the study area found to be contaminated with copper (Cu), iron (Fe), lead (Pb), and chromium (Cr) while low contamination of zinc (Zn) and arsenic (As) was found according to heavy metal evaluation index (HEI). High contamination of chromium (HPI= 9740.8) and lead (HPI=188) was recorded as per HPI. HQ value for men, women, and children in case of zinc were found safe while HQ values for copper and lead in all population groups were found at risk. Overall, the study area was found highly contaminated with the lead, copper, and chromium concentrations. Thus, study recommends regular monitoring of the groundwater of study area as well as treatment before using this water for drinking purposes.

Unresectable stage III non-small cell lung cancer: could durvalumab be safe and effective in real-life clinical scenarios? Results of a single-center experience.

Introduction: The standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by consolidation durvalumab as shown in the PACIFIC trial. The purpose of this study is to evaluate clinical outcomes and toxicities regarding the use of durvalumab in a real clinical scenario. Methods: A single-center retrospective study was conducted on patients with a diagnosis of unresectable stage III NSCLC who underwent radical CRT followed or not by durvalumab. Tumor response after CRT, pattern of relapse, overall survival (OS) and progression-free survival (PFS), and toxicity profile were investigated. Results: Eighty-five patients met the inclusion criteria. The median age was 67 years (range 45-82 years). Fifty-two patients (61.2%) started sequential therapy with durvalumab. The main reason for excluding patients from the durvalumab treatment was the expression of PD-L1 < 1%. Only two patients presented a grade 4 or 5 pneumonitis. A median follow-up (FU) of 20 months has been reached. Forty-five patients (52.9%) had disease progression, and 21 (24.7%) had a distant progression. The addition of maintenance immunotherapy confirmed a clinical benefit in terms of OS and PFS. Two-year OS and PFS were respectively 69.4% and 54.4% in the durvalumab group and 47.9% and 24.2% in the no-durvalumab group (p = 0.015, p = 0.007). Conclusion: In this real-world study, patients treated with CRT plus durvalumab showed clinical outcomes and toxicities similar to the PACIFIC results. Maintenance immunotherapy after CRT has been shown to be safe and has increased the survival of patients in clinical practice.

A Single-Center Case Series of Successful Abdominal Organ Transplantation From SARS-CoV-2-infected Donors to Uninfected Recipients-Do We Need Rigorous Monitoring?

There is limited documentation of hematogenous transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in non-lung transplants from infected donors to uninfected recipients. Methods: We analyzed 16 recipients (7 liver, 9 kidney) transplanted from SARS-CoV-2 nucleic acid test+ deceased donors from December 25, 2021, to February 28, 2022, who were followed-up for at least 90 d. Primary outcomes included coronavirus disease 2019-positivity, allograft loss, and all-cause mortality. Secondary outcomes included biopsy-proven rejection (BPAR), donor-specific antibodies, delayed graft function, and opportunistic infections. Unlike previous studies, we followed the recipients clinically with the intent to treat if they developed SARS-CoV-2 symptoms. Results: All donors were SARS-CoV-2 polymerase chain reaction-positive 72 h before donation. No recipients developed SARS-CoV-2 infection. The nadir serum creatinine and estimated glomerular filtration rate were 1.33 mg/dL and 64 mL/min/1.732 m2 for kidney transplantation (KTx) respectively. The median alanine transaminase was 14.5 IU/L, aspartate aminotransferase 13 IU/L, and alkaline phosphatase 74 IU/L. Two KTx patients lost allograft, and 1 liver transplantation patient died with a failed allograft. However, this was unrelated to their SARS-CoV-2-positive donor status. One BPAR in the liver transplantation was treated with steroids. No donor-specific antibodies or BPAR were reported in the KTx. Six KTx patients experienced delayed graft function, and 4 are off dialysis. Two KTx patients developed cytomegalovirus infection because of an error in reporting the cytomegalovirus serostatus by the donor center. We did not do serial testing for SARS-CoV-2 by polymerase chain reaction, imaging, or cycle threshold score pre- or posttransplant for donor/recipient and had comparable outcomes with previous studies. Conclusions: Because of the low risk of transmission, serial testing might not be necessary and, thus, could be reciprocated at small-volume transplant centers.

Anal squamous cell carcinoma: Impact of radiochemotherapy evolution over years and an explorative analysis of MRI prediction of tumor response in a mono-institutional series of 131 patients.

Introduction: Radiochemotherapy (RCHT) for the treatment of anal squamous cell carcinoma (ASCC) has evolved dramatically, also thanks to intensity-modulated RT (IMRT) and 3D image guidance (3D IGRT). Despite most patients presenting fair outcomes, unmet needs still exist. Predictors of poor tumor response are lacking; acute toxicity remains challenging; and local relapse remains the main pattern of failure. Patients and methods: Between 2010 and 2020, ASCC stages I-III treated with 3D conformal radiotherapy or IMRT and CDDP-5FU or Mytomicine-5FU CHT were identified. Image guidance accepted included 2D IGRT or 3D IGRT. The study endpoints included freedom from locoregional recurrence (FFLR), colostomy free survival (CFS), freedom from distant metastasis (FFDM), overall survival (OS), and acute and late toxicity as measured by common terminology criteria for adverse events (CTCAE) version 5.0. An exploratory analysis was performed to identify possible radiomic predictors of tumor response. Feature extraction and data analysis were performed in Python™, while other statistics were performed using SPSS® v.26.0 software (IBM®). Results: A total of 131 patients were identified. After a median FU of 52 months, 83 patients (63.4%) were alive. A total of 35 patients (26.7%) experienced locoregional failure, while 31 patients (23.7%) relapsed with distant metastasis. Five year FFLR, CFS, DMFS and PS resulted 72.3%, 80.1%, 74.5% and 64.6%. In multivariate analysis, 2D IGRT was associated with poorer FFLR, OS, and CFS (HR 4.5, 4.1, and 5.6, respectively); 3DcRT was associated with poorer OS and CFS (HR 3.1 and 6.6, respectively). IMRT reduced severe acute gastro-intestinal (GI) and severe skin acute toxicity in comparison with 3DcRT. In the exploratory analysis, the risk of relapse depended on a combination of three parameters: Total Energy, Gray Level Size Zone Matrix's Large Area High Gray Level Emphasis (GLSZM's LAHGLE), and GTV volume. Conclusions: Advances in radiotherapy have independently improved the prognosis of ASCC patients over years while decreasing acute GI and skin toxicity. IMRT and daily 3D image guidance may be considered standard of care in the management of ASCC. A combination of three pre-treatment MRI parameters such as low signal intensity (SI), high GLSZM's LAHGLE, and GTV volume could be integrated in risk stratification to identify candidates for RT dose-escalation to be enrolled in clinical trials.

Postoperative and Recurrent Hematuria after Pretransplant Core Needle Biopsy in Living Donor Kidney Transplant.

Background: Core needle and wedge biopsies are the two main pathologic ways to determine the suitability of a kidney allograft and to have a baseline allograft biopsy in case of future rejection. Case Presentation. A 57-year-old patient developed a renal arteriovenous fistula causing postoperative and recurrent hematuria after allograft pretransplant renal core needle biopsy and treated with selective Interventional radiology coil embolization. Conclusion: Delayed profound hematuria can be seen after pretransplant core needle renal biopsies and can recur again even after complete resolution, due to arteriovenous fistula formation in the renal calyceal system.

Orthotopic Kidney Transplant as a Fifth Intra-Abdominal Organ after Two Previous Kidney and Two Previous Pancreas Transplants.

Background: Patients with more than two prior kidney transplant procedures pose unique surgical challenges. Once both the right and left retroperitoneal spaces have been dissected, intra-abdominal implantation is usually necessary. If the external iliac arteries have been used previously, it is sometimes necessary to use the aorta and vena cava for implantation. Gaining safe exposure in these cases can be complicated by history of prior laparotomy, adhesive disease, and other surgical histories. Case Presentation. A 58-year-old female with type 1 diabetes and end-stage renal disease presented for surgical evaluation for kidney transplant. Surgical history was notable for prior simultaneous kidney-pancreas transplant followed by both a living donor kidney transplant and a pancreas after kidney transplant. She had undergone both an allograft nephrectomy and an allograft pancreatectomy and currently had a nonfunctioning kidney in the left retroperitoneal position and a nonfunctioning pancreatic allograft on the right common iliac artery. The entire distal aortoiliac system was surgically inaccessible. She was listed for transplantation, and a cadaveric graft was allocated. Intraoperatively, severe lower abdominal and pelvic adhesions prevented any use of the iliac system. A left native nephrectomy was performed, and the allograft was implanted in the left orthotopic position. The native left renal vein was used for outflow, the donor renal artery was joined end-to-side to the infrarenal aorta, and a uretero-ureterostomy was created. The operation was uneventful. The allograft functioned without delay, and almost one year later, the GFR is approximately 50 mg/dL. Conclusion: The left orthotopic position can be a good choice for kidney transplant candidates with histories of prior complex lower abdominal surgery.

Low-dose Lung Radiotherapy for COVID-19-related Pneumonia: Preliminary Results of the Italian Mono-institutional COLOR-19 Trial.

AIM: To evaluate the feasibility and tolerability of low-dose radiotherapy (LDRT) delivered to both lungs in the treatment of SARS-CoV-2-immune-mediated pneumonia in the COLOR-19 study (NCT0437747). PATIENTS AND METHODS: From May 2020 to April 2021 at Brescia University Radiation Oncology Department, three patients with COVID-19-related pneumonia were treated with LDRT according to the COLOR-19 protocol. All patients were treated with a single fraction at the average prescription dose of 0.7 Gy to both lungs. RESULTS: Three patients were enrolled (two males and one female, aged 61-81 years) and underwent LDRT. Despite LDRT being safely performed without significant side-effects, two patients died (one 81-year-old male due to septic shock secondary to Escherichia coli infection and one 79-year-old male, already in poor condition, due to worsening of COVID-19). The remaining female patient (61 years old) underwent LDRT for less severe COVID-19: her clinical condition and chest X-ray improved, and she was discharged home completely asymptomatic 27 days after hospital admission. Blood levels of C-reactive protein and ferritin generally decreased after LDRT. CONCLUSION: Early results of the COLOR-19 study demonstrate the feasibility of LDRT for therapy of COVID-19-related pneumonia; no conclusions on the efficacy have been reached due to poor accrual.

RR Myelo POINT: A Retrospective Single-Center Study Assessing the Role of Radiotherapy in the Management of Multiple Myeloma and Possible Interactions with Concurrent Systemic Treatment.

Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions of concurrent systemic treatment (CST) and RT is limited, and the optimal RT dose is still unclear. Materials and methods: We retrospectively analyzed the records of patients who underwent RT for MM at our institution from 1 January 2005 to 30 June 2020. The data of 312 patients and 577 lesions (treated in 411 accesses) were retrieved. Results: Most of the treated lesions involved the vertebrae (60%) or extremities (18.9%). Radiotherapy was completed in 96.6% of the accesses and, although biologically effective doses assuming an α/ß ratio of 10 (BED 10) > 38 Gy and CST were significantly associated with higher rates of toxicity, the safety profile was excellent, with side effects grade ≥2 reported only for 4.1% of the accesses; CST and BED 10 had no impact on the toxicity at one and three months. Radiotherapy resulted in significant improvements in performance status and in a pain control rate of 87.4% at the end of treatment, which further increased to 96.9% at three months and remained at 94% at six months. The radiological response rate at six months (data available for 181 lesions) was 79%, with only 4.4% of lesions in progression. Progression was significantly more frequent in the lesions treated without CST or BED 10 < 15 Gy, while concurrent biological therapy resulted in significantly lower rates of progression. Conclusion: Radiotherapy resulted in optimal pain control rates and fair toxicity, regardless of BED 10 and CST; the treatments with higher BED 10 and CST (remarkably biological agents) improved the already excellent radiological disease control.

Spinal Stroke following Kidney Transplant.

Complications are a part of surgery. Spinal infarctions are a dreaded complication of aortic surgery. We present a patient who developed a spinal infarct after a kidney transplant. We were unable to find a causative factor in our search for etiology. In our review of the literature, we were unable to find a similar report. We present this case report to highlight a rare complication of kidney transplantation and to reinforce that patients requiring kidney transplant are complex patients with multiple comorbidities that can cause a multitude of complications in the periop period.

Safely Expanding the Liver Donor Pool by Utilization of Organs from Donation after Circulatory Death with Comparable Results to Donation After Brain Death, a Large Single-Center Experience.

BACKGROUND: Use of livers donated after circulatory death (DCD) is one way to expand the donor pool. Our center has aggressively incorporated use of DCD liver grafts into practice. We examined our center and national outcomes as well as national DCD liver utilization. METHODS: Liver transplants performed at our center and nationally from 11/2016 through 9/2020 were compared. Primary outcomes were patient and graft survival, and national DCD liver utilization. RESULTS: For our center, DCD and donation after brain death (DBD) donors were similar except DCD donors were younger (37 vs 40 years; p < 0.05). Recipient Na-MELD (20 vs 24; p < 0.0001) and cold ischemia time (4.63 vs 5.18 h; p < 0.05) were lower in DCD recipients. There were no significant differences in 1-year patient and graft survival between DCD and DBD liver recipients locally. Nationally, there was a difference in 1-year graft survival year (89.4% vs 92.4%, p < 0.0001) but patient survival was similar between groups. The proportion of DCD livers recovered and transplanted widely varied among organ procurement organizations (OPOs) and transplant centers. CONCLUSIONS: Similar outcomes for DCD and DBD liver recipients should encourage centers and OPOs nationwide to expand utilization of DCD livers.

Hepatic Resection and Transplant in Glycogen Storage Diseases.

Patients with glycogen storage diseases pose unique management challenges to clinicians.These challenges are exacerbated wheneverthey undergo surgery as the basic anomaly in their glycogen storage pathways make them susceptible to organic acidosis, which may in turn complicate their preoperative, intraoperative, and postoperative course. Because of the rarity of these diseases, clinicians may not be aware of the specific management concerns. In the case reported here, a 37-year-old patient with glycogen storage disease type 1 underwentleft hepatectomy for hepatic adenomatosis, which was complicated by intraoperative severe lactic acidosis that was successfully treated. After successful hepatectomy, the patient underwent liver transplant without major lactic acidosis or hemodynamic instability. Early recognition and aggressive management of blood sugar and lactic acidosis in patients with glycogen storage diseases can allow for successful outcomes even when complex surgical procedures are required.

Liver Transplant for Management of Hepatic Complications of Dyskeratosis Congenita: A Case Report.

Dyskeratosis congenita, a rare genetic disorder typified by progressive bone marrow failure, is classically characterized by the triad of abnormal skin pigmentation, nail dystrophy, and oral leukoplakia; however, it is a multisystem disease. Although hepatic involvement occurs in about 7% of patients with dyskeratosis congenita, end-stage liver disease is rare. Treatment of dyskeratosis congenita generally involves hematopoietic stem cell transplant. For patients with hepatic failure, liver transplant can be an option. Here, we describe a case of a patient with dyskeratosis congenita who presented with liver failure and pulmonary failure, precluding him from hematopoietic stem cell transplant. After liver transplant, the patient had significant improvements in pulmonary function and transfusion requirements, allowing the patient to qualify for hematopoietic stem cell transplant. Although hematopoietic stem cell transplant is typically the first step in the management of dyskeratosis congenita, for patients with severe hepatic manifestations of the disease, a liver transplant first approach may result in better disease management.

Machine perfusion of kidney allografts affects early but not late graft function.

BACKGROUND: Hypothermic machine perfusion (HMP) parameters are influenced by donor variables which further affect recipient outcome. Interplay between these parameters can help to predict kidney performance on pump and the long term outcome. METHODS: All the kidneys transplanted at our center between May 2013 through November 2017 were included in the study. Donor and recipient data was obtained from internal database. Multiple logistic regression models with backward selection were used to determine significant donor and pump variables. RESULTS: Donor BMI, KDPI, age and donor sex had a significant association with pump flow. Donor sex, donor type, KDPI and age had significant effect on RI. Diastolic pressure and KDPI were significantly associated with DGF. Duration on pump, KDPI, flow, donor creatinine and type of donor were significantly associated with day 5 creatinine. KDPI was significantly associated with Day 365 creatinine. CONCLUSION: HMP effects early graft function while the long term function depends on donor parameters.

Short-term grazing of cover crops and maize residue impacts on soil greenhouse gas fluxes in two Mollisols.

An integrated crop-livestock system (ICLS), when managed properly, can help in mitigating soil surface greenhouse gas (GHG) fluxes, especially carbon dioxide (CO2 ), methane (CH4 ), and nitrous oxide (N2 O). However, the impacts of an ICLS on GHG fluxes are poorly understood. The present study was conducted at two sites (northern Brookings [Brookings-N] and northwestern Brookings [Brookings-NW]) established in 2016 and 2017, respectively, under loamy soils in South Dakota. The specific objective was to evaluate the impact of cover crops (CCs) and grazed CCs under oat (Avena sativa L.)-CCs-maize (Zea mays L.) rotation on GHG fluxes. Study treatments included the following: (a) a legume-dominated CC (LdC), (b) a cattle-grazed LdC (LdC+G), (c) a grass-dominated CC (GdC), (d) a cattle-grazed GdC (GdC+G), and (e) one without CC or grazing (NC). Greenhouse gas monitoring occurred weekly during the growing crop seasons in 2016 and 2017 for Brookings-N and in 2017 and 2018 for Brookings-NW. Data showed that cumulative CO2 and N2 O fluxes at Brookings-N were lower for GdC+G (4042 kg C ha-1 for CO2 and 1499 g N ha-1 for N2 O) than for LdC+G (4819 kg C ha-1 for CO2 and 2017 g N ha-1 for N2 O), indicating the superiority of GdC+G over LdC+G in reducing GHG fluxes. However, no effect from grazed CC on cumulative CO2 and N2 O fluxes were observed at the Brookings-NW site. Cumulative CH4 flux was not affected by an ICLS at either site. This short-term investigation showed that, in general, CCs and grazing of CCs and maize residue did not impact GHG fluxes.

A Study of Artificial Sweeteners and Thyroid Cancer Risk.

BACKGROUND: In recent decades, data from certain observational studies have stirred controversy over artificial sweeteners by linking them with certain malignancies. As the incidences of artificial sweetener consumption and thyroid cancer are both increasing, our study aimed to determine any possible association between them. METHODS: This retrospective observational study enrolled 50 patients (group 1) with proven diagnosis of well-differentiated thyroid cancer (WDTC) and 50 control subjects (group 2) diagnosed as having benign thyroid nodule by fine-needle aspiration. The survey questionnaire included the total amount and duration of intake of artificial sweeteners. RESULTS: Increased consumption of artificial sweeteners was noted in group 1 as compared to group 2, which was statistically significant (76% vs. 24%, P < 0.01). This study suggested that the use of an average of four packets (4 g) per day of artificial sweetener for an average duration of 5 years is associated with WDTC. CONCLUSIONS: Our study emphasizes the significance of artificial sweetener consumption as a potential risk factor for WDTC and increase in public awareness regarding this association if other studies in future report similar findings.

Complete response with anti-PD-L1 antibody following progression on anti-PD-1 antibody in advanced non-small cell lung cancer.

Immune-checkpoint inhibitors (ICI), specifically inhibitors of programmed death ligand-1 (PD-L1) and receptor (PD-1) are the new standard of care for the treatment of patients with advanced non-small cell lung cancer (NSCLC) in front line setting as monotherapy or along with chemotherapy. Many of these agents are also approved for use in subsequent lines of treatment on progression on platinum doublet chemotherapy. Nivolumab, pembrolizumab and atezolizumab are currently approved ICI for advanced NSCLC. To date, no study has reported efficacy and safety of alternate PD-1/PD-L1 inhibitors in patients with NSCLC who have progressed on one ICI. Here, we report a case of a patient with advanced NSCLC who had a complete response to atezolizumab, following progression of disease on platinum doublet chemotherapy and then, nivolumab monotherapy.

Leukostasis in Chronic Lymphocytic Leukemia.

BACKGROUND Chronic lymphocytic leukemia (CLL) is a mature B cell lymphocytic neoplasm that has an indolent clinical course. Therefore, not all patients with CLL require treatment at the time of diagnosis. Hyperleukocytosis (white blood cell count, >100×109/L) is present in a large proportion of patients with CLL. However, symptomatic hyperleukocytosis (leukostasis) is an extremely uncommon presentation of CLL. Leukostasis frequently presents with the clinical manifestation of respiratory, neurological, or renal system problems. This is secondary to the decreased tissue perfusion due to the intravascular accumulation of large aggregates of leukemic cells. Leukostasis is a medical emergency requiring intensive care unit (ICU) admission and its management includes aggressive hydration, prevention and treatment of tumor lysis syndrome, cytoreduction, and leukapheresis. CASE REPORT We report a case of a 77-year-old woman with a long history of untreated CLL who presented with respiratory symptoms with hyperleukocytosis. Her condition rapidly deteriorated, requiring intubation. She required induction chemotherapy with chlorambucil as well as 2 sessions of leukapheresis, to which she responded well. In most reported leukostasis cases in the literature, the white blood cell (WBC) count was >1000×109/L. We present a case of a patient with leukostasis with WBC count 524×109/L who responded to chlorambucil and leukapheresis, with good recovery. CONCLUSIONS Leukostasis, although extremely rare, is a life-threatening complication in patients with CLL. It should be strongly considered in the differential diagnosis of patients with CLL who present with hyperleukocytosis and acute pulmonary symptoms. Clinicians should be aware of this medical emergency, as delayed treatment can increase morbidity and mortality.