Renal-Limited Thrombotic Microangiopathy in a Patient Who Received Gemcitabine, Ramucirumab, and Pembrolizumab: A Case Report and Literature Review.

Cancer drug-induced thrombotic microangiopathy (DITMA) is an important and serious cause of kidney disease in cancer patients. In addition to classical chemotherapy, the increasing use of targeted therapy and immunotherapy has led to more oncotherapy-associated thrombotic microangiopathy (TMA). It is important for clinicians to recognize this potentially life-threatening adverse effect and gain knowledge of the patient's clinical course and treatment response. In this paper, we report a patient with lung cancer, who was treated with three different classes of anti-neoplastic agents, gemcitabine, ramucirumab, and pembrolizumab. This patient subsequently developed renal-limited thrombotic microangiopathy(rTMA) requiring hemodialysis. The varying features of TMA caused by these therapies were discussed. We also described the clinical course, diagnostic challenges, and management of this patient.

High Tidal Volume, High Positive End Expiratory Pressure and Apneic Breath Hold Strategies (Lung Navigation Ventilation Protocol) With Cone Beam Computed Tomography Bronchoscopic Biopsy of Peripheral Lung Lesions: Results in 100 Patients.

BACKGROUND: A dedicated anesthesia protocol for bronchoscopic lung biopsy-lung navigation ventilation protocol (LNVP)-specifically designed to mitigate atelectasis and reduce unnecessary respiratory motion, has been recently described. LNVP demonstrated significantly reduced dependent ground glass, sublobar/lobar atelectasis, and atelectasis obscuring target lesions compared with conventional ventilation. METHODS: In this retrospective, single-center study, we examine the impact of LNVP on 100 consecutive patients during peripheral lung lesion biopsy. We report the incidence of atelectasis using cone beam computed tomography imaging, observed ventilatory findings, anesthesia medications, and outcomes, including diagnostic yield, radiation exposure, and complications. RESULTS: Atelectasis was observed in a minority of subjects: ground glass opacity atelectasis was seen in 30 patients by reader 1 (28%) and in 18 patients by reader 2 (17%), with good agreement between readers (κ = 0.78). Sublobar/lobar atelectasis was observed in 23 patients by reader 1 and 26 patients by reader 2, also demonstrating good agreement (κ = 0.67). Atelectasis obscured target lesions in very few cases: 0 patients (0%, reader 1) and 3 patients (3%, reader 2). Diagnostic yield was 85.9% based on the AQuIRE definition. Pathology demonstrated 57 of 106 lesions (54%) were malignant, 34 lesions (32%) were benign, and 15 lesions (14%) were nondiagnostic. CONCLUSION: Cone beam computed tomography images confirmed low rates of atelectasis, high tool-in-lesion confirmation rate, and high diagnostic yield. LNVP has a similar safety profile to conventional bronchoscopy. Most patients will require intravenous fluid and vasopressor support. Further study of LNVP and other ventilation protocols are necessary to understand the impact of ventilation protocols on bronchoscopic peripheral lung biopsy.

Pearls and pitfalls of PROMIS clinically significant outcomes in orthopaedic surgery.

INTRODUCTION: Patient-Reported Outcome Measurement Information System (PROMIS) was developed as a uniform and generalizable PROM system using item response theory and computer adaptive testing. We aimed to assess the utilization of PROMIS for clinically significant outcomes (CSOs) measurements and provide insights into its use in orthopaedic research. MATERIALS AND METHODS: We reviewed PROMIS CSO reports for orthopaedic procedures via PubMed, Cochrane Library, Embase, CINAHL, and Web of Science from inception to 2022, excluding abstracts and missing measurements. Bias was assessed using the Newcastle-Ottawa Scale (NOS) and questionnaire compliance. PROMIS domains, CSO measures, and study populations were described. A meta-analysis compared distribution and anchor-based MCIDs in low-bias (NOS ≥ 7) studies. RESULTS: Overall, 54 publications from 2016 to 2022 were reviewed. PROMIS CSO studies were observational with increasing publication rates. Evidence-level was II in 10/54, bias low in 51/54, and compliance ≥ 86% in 46/54. Most (28/54) analysed lower extremity procedures. PROMIS domains examined Pain Function (PF) in 44/54, Pain Interference (PI) in 36/54, and Depression (D) in 18/54. Minimal clinically important difference (MCID) was reported in 51/54 and calculated based on distribution in 39/51 and anchor in 29/51. Patient acceptable symptom state (PASS), substantial clinical benefit (SCB), and minimal detectable change (MDC) were reported in ≤ 10/54. MCIDs were not significantly greater than MDCs. Anchor-based MCIDs were greater than distribution based MCIDs (standardized mean difference = 0.44, p < 0.001). CONCLUSIONS: PROMIS CSOs are increasingly utilized, especially for lower extremity procedures assessing the PF, PI, and D domains using distribution-based MCID. Using more conservative anchor-based MCIDs and reporting MDCs may strengthen results. Researchers should consider unique pearls and pitfalls when assessing PROMIS CSOs.

Megadose Vitamin C Prescription Through Alternative Medicine Leading to End-Stage Renal Disease: Case Study and Literature Review.

Modern medicine has made tremendous advancements and succeeded in increasing longevity through adequate screening and diagnosis and various new therapeutic approaches. However, alternative medicine is a branch of health care practicing different traditional and unconventional, potentially hazardous therapies to treat commonly known ailments. Standard low-dose vitamin C, ie, 500-1000 mg, is approved in medical conditions like methemoglobinemia, scurvy, burns and also helps iron absorption in anemia. However, toxic doses carry high nephrotoxicity potential like in our case. We present a 74-year-old Caucasian female falling victim to one such alternative therapy leading to acute kidney injury requiring lifelong hemodialysis. She had endometrial cancer and received 100 gm of intravenous vitamin C weekly through a provider for the last 6 weeks as part of this alternate approach to cure her cancer. Upon admission, the serum creatinine level was elevated at 8.2 mg/dl, which subsequently did not improve with conservative management. Renal biopsy revealed diffuse acute tubular injury with polarized microscopy demonstrating calcium oxalate crystals. While her blood vitamin C levels were high, the serum oxalate level was normal. She ended up requiring renal replacement therapy permanently. Alternative medicine continues to be a significant health care hazard with the potential to cause unwanted irreversible nephrotoxicity. Public attention is necessary at various social levels to counter the detrimental outcomes of alternative medicine.

Risk Factors for Nonunion Following Ankle Arthrodesis: A Systematic Review and Meta-analysis.

BACKGROUND: Nonunion is a postoperative complication after ankle arthrodesis (AA), which leads to increased morbidity and revision rates. Previous studies have identified risk factors for nonunion following AA, but no meta-analysis has been performed to stratify risk factors based on strength of evidence. METHODS: Abstracts and full-text articles were screened by 2 independent reviewers. Relevant data were extracted from the included studies. Random effects meta-analyses were summarized as forest plots of individual study and pooled random effect results. RESULTS: Database search yielded 13 studies involving 987 patients were included, and 37 potential risk factors for nonunion. Meta-analysis found 5 significant risk factors for nonunion post-AA. Strong evidence supports male gender (OR: 1.96; 95% CI: 1.13-3.41), smoking (OR: 2.89; 95% CI: 1.23-6.76), and history of operative site infection prior to arthrodesis (OR: 2.40; 95% CI: 1.13-5.09) as predictors for nonunion following AA. There was moderate evidence supporting history of open injury (OR: 5.95; 95% CI: 2.31-15.38) and limited evidence for preoperative avascular necrosis (OR: 13.16; 95% CI: 2.17-79.61) as possible risk factors for nonunion. CONCLUSION: The results of our meta-analysis suggest that male gender, smoking, and history of operative site infection have strong evidence and that history of open injury and avascular necrosis also have evidence as risk factors for nonunion. Surgeons should be cognizant of these risks when performing AA and closely follow up with patients with the aforementioned risk factors to ensure postoperative success. LEVELS OF EVIDENCE: Level V: Systematic review of cohort and case-control studies.

Increasing Patient Age, Ambulatory Surgery Center Setting, and Surgeon Experience Are Associated With Shorter Operative Duration for Anterior Cruciate Ligament Reconstruction.

Purpose: To identify variables associated with operative duration and intraoperative or perioperative complications after primary anterior cruciate ligament reconstruction (ACLR). Methods: Surgeons who performed a minimum of 20 arthroscopic cases per month were recruited for participation through the Arthroscopy Association of North America from 2011 through 2013. All participants agreed to voluntarily submit data for 6 months of consecutive knee and shoulder arthroscopy cases. Only subjects coded for ACLR were analyzed, whereas revision cases were excluded. ACLRs were subdivided into isolated ACLR, ACLR with minor concomitant procedures, and ACLR with major concomitant procedures. Patient, surgeon, and surgical variables were analyzed for their effect on operative duration and complications. Results: One hundred thirty-five orthopaedic surgeons participated, providing 1,180 primary ACLRs (399 isolated ACLRs, 441 ACLRs plus minor procedures, and 340 ACLRs plus major procedures). Most surgeons were in private practice (72.8%). Most patients were male patients (58.8%), and the mean body mass index (BMI) was 26.2 ± 5.1. The overall mean operative duration was 95.9 ± 42.0 minutes (isolated ACLRs, 88.4 ± 36.8 minutes; ACLRs plus minor concomitant procedures, 90.1 ± 37.6 minutes; and ACLRs plus major concomitant procedures, 118.5 ± 112.4 minutes; P < .001). Patient age was inversely correlated with operative duration (ρ = -0.221, P < .001). Surgical procedures performed in an ambulatory surgery center had a shorter mean operative duration (91.5 ± 40.4 minutes) compared with those performed in a hospital setting (105.0 ± 43.8 minutes, P < .001). There were 22 intraoperative and 47 early postoperative complications, with the most common being deep vein thrombosis (n = 15). Surgical volume (knee arthroscopy cases per month) correlated inversely with operative time (ρ = -0.200, P = .001) and complication rate (ρ = -0.112, P < .001). Patient BMI was associated with increased odds of early postoperative complications on multivariate analysis (odds ratio, 1.060; P = .044; 95% confidence interval, 1.002-1.121). Conclusions: Increasing patient age, private practice, ambulatory surgery center setting, and surgeon experience are associated with a shorter operative duration for ACLR. Although an increasing number of arthroscopic knee procedures performed by surgeons correlated with fewer complications, only increasing patient BMI significantly predicted odds of complications. Level of Evidence: Level IV, prognostic case series.

Do Outcomes of Meniscal Allograft Transplantation Differ Based on Age and Sex? A Comparative Group Analysis.

PURPOSE: To analyze the effect of patient age, sex, and associated preoperative factors on patient-reported outcome (PRO) measures and graft survival following primary meniscal allograft transplantation (MAT). METHODS: A prospectively collected database was retrospectively reviewed to identify patients who underwent primary MAT with a minimum of 2 years of follow up between 1999 and 2017. Demographic, intraoperative, and postoperative outcome data were collected for each patient. Postoperative outcomes were stratified based on age and sex, and comparative statistical analysis was performed between sexes, both >40 and <40. RESULTS: A total of 238 patients underwent primary MAT during the study period, of which 212 patients (mean age, 28.5 ± 9.0 years; range, 15.01-53.67 years) met the inclusion criteria with a mean follow-up of 5.1 ± 3.4 years (range 2.0-15.9 years). At final follow-up, patients ≥40 and <40 years of age demonstrated statistically significant improvements in nearly all PRO scores (P < .05 for both groups). There were no significant differences between either group for achievement of minimal clinically important difference for International Knee Documentation Committee (P = .48) or Knee Injury and Osteoarthritis Outcome Score symptoms (P = .76). Because of insufficient numbers, a statistically significant difference could not be demonstrated in reoperation rate (≥40: 1.49 ± 1.77 years, <40: 1.87 ± 1.98 years, P = .591), failure rate (≥40: 7/32 [21.9%], <40: 19/180 [10.6%], P = .072), or complication rate (≥40: 2/32 [6.3%], <40: 12/180 [6.7%], P = .930) based on age. Both sexes showed a significant improvement in PROs, whereas female patients were more likely to undergo revision surgery (P = .033), with no significant differences based on time to reoperation, failure, or complication rates. CONCLUSIONS: PROs similarly improved following MAT in both patients aged ≥40 and those <40 at final follow-up with no significant differences in minimal clinically important difference achievement rate, complication rate, reoperation rate, time to reoperation, or failure rate between groups. Female patients may be more likely to undergo revision surgery after MAT. LEVEL OF EVIDENCE: III; therapeutic retrospective comparison study.

Risk factors for nonunion following tibiotalocalcaneal arthrodesis: A systematic review and meta-analysis.

BACKGROUND: The goal of this study is to review the literature to identify risk factors for nonunion after tibiotalocalcaneal arthrodesis (TTCA) and stratify them based on strength of evidence. METHODS: Five databases were searched from inception to May 17th, 2020. Abstracts and full-text articles were screened for those that included risk factors predictive of nonunion following TTCA. RESULTS: Eight studies involving 624 patients were included and 33 potential risk factors for nonunion were identified. Strong evidence supported prior peripheral neuropathic conditions as risk factors for nonunion following surgery (OR: 2.86, 95% CI: 1.56-5.23). CONCLUSION: TTCA is an effective salvage procedure but is associated with high nonunion rates. The results of our meta-analysis suggest that prior peripheral neuropathic conditions have strong evidence for failure to achieve union. Surgeons should be cognizant of these risks when performing TTCA and carefully monitor patients with the aforementioned comorbidity to achieve successful results.

Defining Clinically Significant Outcomes Following Superior Capsular Reconstruction With Acellular Dermal Allograft.

PURPOSE: To define clinically significant outcomes (CSO) thresholds for minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient-acceptable symptomatic state (PASS) in patients undergoing superior capsular reconstruction (SCR) with an acellular dermal allograft. We also evaluated patient-specific variables predictive of achieving CSO thresholds. METHODS: The American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), Single Assessment Numeric Evaluation (SANE), and subjective Constant-Murley (Constant) scores were collected preoperatively and at the most recent follow up for patients undergoing SCR from 2010 to 2019. A distribution-based approach was used to calculate MCID, and an anchor-based approach was used to calculate SCB and PASS. Logistic regression was used to determine factors associated with CSO achievement. RESULTS: Fifty-eight patients were identified (n = 39 males; n = 19 females) with a mean age of 53.4 ± 14.1 years at surgery and an average follow-up of 23 months. The MCID, SCB, and PASS were 11.2, 18.02, and 68.82 for ASES, 14.5, 23.13, and 69.9 for SANE, and 3.6, 10, and 18 for Constant, respectively. Subscapularis tear, female sex, and workers compensation (WC) status reduced odds of achieving MCID. Reduced odds of achieving Constant SCB were associated with older age, female sex, and WC status, while concomitant distal clavicle excision during SCR and lower preoperative ASES increased odds of achieving ASES SCB. Reduced odds for achieving ASES PASS were associated with female sex and WC status, while reduced odds for achieving SANE PASS were associated with subscapularis tearing preoperatively. CONCLUSION: On the basis of calculated values for MCID, SCB, and PASS, subscapularis tearing, WC status, age, and sex are associated with failure to achieve clinically significant outcomes following SCR. Concomitant distal clavicle excision during SCR and lower preoperative ASES was predictive for achievement of MCID and SCB. By defining the thresholds and variables predictive of achieving CSOs following SCR, surgeons may better counsel patients prior to SCR. LEVEL OF EVIDENCE: Level IV, case series.

Hyponatremia and Fever in a Patient on Ipilimumab and Nivolumab (Immune Checkpoint Inhibitors): A Case Report.

Immune checkpoint inhibitors (ICIs) are novel anticancer therapy approved in multiple tumors and their use is rapidly increasing. They are associated with various systemic side effects that are immune-mediated and clinically coined as "immune-related adverse effects" (irAE). Hyponatremia is a possible side effect in patients receiving ICIs. Fever is another side effect that is mostly non-infectious. There are different mechanisms leading to hyponatremia in patients on ICIs, which could be (1) hypovolemic hyponatremia due to hemodynamic disturbance secondary to volume depletion (eg, from irAE like colitis and enteritis) or hypervolemia due to congestive heart failure, cirrhosis, or nephrosis; (2) syndrome of inappropriate antidiuretic hormone (SIADH) secretion (especially from underlying lung cancer or neurological irAE like encephalitis and meningitis) with elevated urine sodium and urine osmolarity; and (3) irAE-related endocrinopathies such as hypophysitis, adrenal insufficiency, and hypothyroidism leading to euvolemic hyponatremia. We describe an interesting case of hyponatremia and fever in a patient receiving Ipilimumab and Nivolumab. The possible etiology of hyponatremia, in this case, was hypovolemia and volume depletion secondary to fever.

Comparison of 4 tests' utility for predicting need for emergency department care in patients with alcohol-related complaints.

INTRODUCTION: Intoxication is a common presenting complaint in emergency departments (ED), but many patients with intoxication do not need emergency care. Three screens (BLINDED, Brown, and San Francisco) attempt to determine which intoxicated patients can be triaged to a lower level of care. METHODS: Observational multi-center cohort study of patients presenting to one of three ED with complaints consistent with acute intoxication. When a qualifying patient was brought to the emergency department, a team member interviewed the triaging provider. Interviews covered all three screens and the provider's gestalt. Receiver operating curve (ROC) analysis was used to determine which screen performed best. Cases were reviewed to determine need for emergency care. RESULTS: Of the 199 subjects studied, 91% (181/199) were male and were 50 years old on average (SD = 12 years). Of the 55 subjects tested (28%), their average alcohol level was 251 mg/dL (SD = 146 mg/dL). Only 117 subjects (59%) had complete information for inclusion in the final comparison of screens. Provider gestalt performed best (AUC = 0.69), but there were no meaningful differences between any of the screens (AUC = 0.62-0.66, p > 0.05 for all comparisons). Inability to sit up was sensitive for needing emergent care (88%), but it was non-specific (17%). Similarly, signs of trauma were specific (99%) for ED care, but insensitive (18%). CONCLUSIONS: The three formal screens and provider gestalt performed similarly.

Osteochondral Allograft Transplant for Focal Cartilage Defects of the Femoral Condyles: Clinically Significant Outcomes, Failures, and Survival at a Minimum 5-Year Follow-up.

BACKGROUND: Osteochondral allograft (OCA) transplant for symptomatic focal cartilage defects in the knee has demonstrated favorable short- to midterm outcomes. However, the reoperation rate is high, and literature on mid- to long-term outcomes is limited. PURPOSE: To analyze clinically significant outcomes (CSOs), failures, and graft survival rates after OCA transplant of the femoral condyles at a minimum 5-year follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Review of a prospectively maintained database of 205 consecutive patients who had primary OCA transplant was performed to identify patients with a minimum of 5 years of follow-up. Outcomes including patient-reported outcomes (PROs), CSOs, complications, reoperation rate, and failures were evaluated. Failure was defined as revision cartilage procedure, conversion to knee arthroplasty, or macroscopic graft failure confirmed using second-look arthroscopy. Patient preoperative and surgical factors were assessed for their association with outcomes. RESULTS: A total of 160 patients (78.0% follow-up) underwent OCA transplant with a mean follow-up of 7.7 ± 2.7 years (range, 5.0-16.3 years). Mean age at the time of surgery was 31.9 ± 10.7 years, with a mean symptom duration of 5.8 ± 6.3 years. All mean PRO scores significantly improved, with 75.0% of patients achieving minimal clinically important difference (MCID), and 58.9% of patients achieving significant clinical benefit for the International Knee Documentation Committee score at final follow-up. The reoperation rate was 39.4% and was associated with a lower probability of achieving MCID. However, most patients undergoing reoperation did not proceed to failure at final follow-up (63.4% of total reoperations). A total of 34 (21.3%) patients had failures overall, and the 5- and 10-year survival rates were 86.2% and 81.8%, respectively. Failure was independently associated with greater body mass index, longer symptom duration, number of previous procedures, and previous failed cartilage debridement. Athletes were protected against failure. Survival rates over time were not affected by OCA site (P = .154), previous cartilage or meniscal procedure (P = .287 and P = .284, respectively), or concomitant procedures at the time of OCA transplant (P = .140). CONCLUSION: OCA transplant was associated with significant clinical improvement and durability at mid- to long-term follow-up, with 5- and 10-year survival rates of 86.2% and 81.8%, respectively. Maintenance of CSOs can be expected in the majority of patients at a mean of 7.7 years after OCA transplant. Although the reoperation rate was high (39.4%) and could have adversely affected chances of maintaining MCID, most patients did not have failure at long-term follow-up.

Anti-interleukin (IL)-5 as a steroid-sparing agent in chronic eosinophilic pneumonia.

Introduction: Anti-interleukin (IL)-5 therapy is a novel drug class clinically effective in patients with diverse eosinophil-related disorders such as allergic eosinophilic asthma, eosinophilic granulomatosis with polyangiitis (EGPA), nasal polyposis, eosinophilic COPD, and other non-pulmonary disorders such as eosinophilic esophagitis. Chronic eosinophilic pneumonia (CEP) is a steroid responsive disorder, however, relapses are common following corticosteroid tapering. Case Study: We present the case of a 42-year-old woman with steroid-dependent relapsing CEP successfully treated with anti-IL-5 antibody. Results: Treatment with anti-IL-5 antibody resulted in remission with the ability to taper off the steroids, and no recurrence of the disease for 6 months. Conclusion: Our case report supports the potential use of anti-IL-5 therapy for remission of patients with CEP with recurrent relapses. Whether, it would also be an effective initial therapy might also be an area that deserves future investigation.

A rare systemic etiology of heart failure and liver dysfunction.

Systemic amyloidosis is a rare condition that can manifest with cardiomyopathy, hepatic dysfunction, and renal disease. Diagnosis is often missed and/or delayed due to chronic multi-system involvement and indeterminate signs and symptoms. Treatment generally involves systemic therapy and autologous stem-cell transplantation.

Incidental Finding of Bronchopulmonary Sequestration in a 64-Year-Old Female.

BACKGROUND: Bronchopulmonary sequestration is a congenital abnormality of the primitive foregut. In adults, the typical age at presentation is 20-25 years. CASE REPORT: A 64-year-old female was referred for evaluation of an 8 × 6-cm right lower lobe cystic lesion. Her medical history was significant for recurrent right lower lobe pneumonia requiring multiple hospitalizations. Her physical examination was significant for crackles at the right lung base. Computed tomography (CT) of the chest with contrast showed cystic changes with thickened septation of the medial segment of the right lower lobe lacking distinct visceral pleura and with arterial supply from the anomalous branch of the thoracic aorta arising near the celiac trunk. Pulmonary angiography confirmed the diagnosis of intralobar pulmonary sequestration. The patient underwent celiac endovascular coil embolization of the anomalous artery to lessen the risk of hemorrhage prior to video-assisted thoracoscopic surgery (VATS) resection of the right lower lobe. She recovered well and was discharged home 1 week after VATS lobectomy. Follow-up CT of the chest 2 months later showed normal postsurgical changes related to right lower lobe lobectomy. The patient remained asymptomatic and resumed her daily activities. CONCLUSION: Pulmonary sequestration can present with recurrent pneumonia in late adulthood. Physicians must review any previous imaging studies of the chest to identify the structural abnormality and be cognizant of differential diagnoses such as infected cystic bronchiectasis, bronchogenic cyst, congenital diaphragmatic hernia, or cystic adenomatoid malformation that can occur in conjunction with bronchopulmonary sequestration. Pulmonary angiogram is the gold standard to confirm the diagnosis of bronchopulmonary sequestration. Surgical resection is the standard of care.

Endobronchial lipoma causing progressive dyspnea.

We describe a 63-year-old male who presented with progressive exertional dyspnea, post-obstructive pneumonia and chest CT findings of an endobronchial lesion. Bronchoscopy revealed an endobronchial lipoma, which was resected using snare electrocautery. Complete resolution of the patient's symptoms was noted following bronchoscopic resection.