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Non-muscle-invasive bladder cancer is one of the most common malignancies. Patients with intermediate-risk or high-risk disease can be treated with intravesical Bacillus Calmette-Guerin, a vaccine against tuberculosis. However, many of these patients will experience tumor recurrence, despite appropriate treatment. 1 The standard of care in these patients is radical cystectomy (RC) with urinary diversion. 2 Patients diagnosed with muscle-invasive bladder cancer (MIBC) have traditionally faced 2 main treatment options: RC and urinary diversion, as in Bacillus Calmette-Guerin-unresponsive Non-muscle-invasive bladder cancer, or alternatively, trimodal therapy comprising maximal transurethral resection of bladder tumor plus chemoradiation. 3 For patients with MIBC and clinical (c)T2-T4a, neoadjuvant chemotherapy (NAC) preceding RC is supported by Level 1 evidence with a modest 5-year overall survival benefit of 5% with cisplatin-based regimens. 4-9 A number of factors preclude MIBC patients from standard treatment options. For example, patients with serious comorbidities might be unable to tolerate general anesthesia, while others might be unwilling to adapt to the lifestyle changes after RC. 10-12 Likewise, patients with extensive carcinoma in situ or poor bladder function might not be optimal candidates for trimodal therapy or be prepared for the ongoing risk that salvage RC might be ultimately required. Reasons for the underuse of NAC range from the fear of delaying potentially curative surgery in nonresponders to patient ineligibility to cisplatin-based NAC. 13,14 Despite best efforts, in both surgical and bladder-sparing approaches, the 5-year overall survival in treated patients with MIBC is only 35% to 50%. 3,15 Strategies to improve overall prognosis as well as to reduce the indications of RC are desperately needed. Trial results have demonstrated the unprecedented ability of immune-checkpoint inhibitors to induce durable remissions in some patients with metastatic urothelial carcinoma. 16-20 Furthermore, immune-checkpoint inhibitors have shown to be better tolerated than traditional chemotherapy. 16 These successful results have spearheaded the research on these agents in earlier curative settings, with the shared goal of improving overall outcomes, and potentially avoid surgery in patients who show complete response (pT0). Strategies to enhance the immune response by combining immunotherapy with immune sensitizers such as chemotherapy, immunotherapy, targeted therapy or radiation are on the rise.

Nilotinib is used as standard treatment in managing chronic myeloid leukaemia (CML). A 23-year-old man with CML and on nilotinib was admitted to the intensive care unit due to respiratory failure. Three years prior, he developed pleural effusion from dasatinib therapy thus, his CML regimen was changed to nilotinib. Although the pleural effusion had once improved, the chest imaging revealed left-dominant bilateral pleural effusion. Endotracheal intubation and left thoracic drainage were performed. Nilotinib treatment was discontinued, and approximately 60 hours later, nilotinib concentrations of 927 and 2092 ng/mL were determined in his blood and pleural effusion, respectively. Severe pleural effusion may be induced in patients administering nilotinib, and nilotinib concentrations in blood and pleural effusion can be elevated in patients with nilotinib-related pleural effusion. Cross-occurrence of pleural effusions needs to be monitored precisely, especially in patients who are switched to other tyrosine kinase inhibitors after dasatinib treatment.

Introduction Manual therapy has been shown to reduce self-reported symptoms in patients with chronic tension-type headache (CTTH). However, simultaneous application of suboccipital muscle inhibition and interferential current has not previously been investigated. This study evaluates the effectiveness of combined treatment with suboccipital muscle inhibition and interferential current compared to standard treatment for pain, disability, and headache impact in patients with CTTH. Methods Patients were randomly allocated to receive either standard treatment (n = 13) or the experimental treatment (n = 12), consisting of 20 minutes of suboccipital muscle inhibition plus interferential current twice weekly for 4 weeks. The primary outcome was improvement in pain, and secondary outcomes included improvement in headache-related disability and reduction in headache impact, which were assessed at baseline and at 4 weeks by a blinded rater. Results Statistical analysis showed improvements in the experimental treatment group at 4 weeks for headache-related disability (Neck Disability Index: Hedges' g = 1.01, P = .001; and Headache Disability Inventory: Hedges' g = 0.48, P = .022) and headache impact (6-item Headache Impact Test: Hedges' g = 0.15, P = .037) but not for self-reported pain (numerical rating scale: Hedges' g = 1.13, P = .18). Conclusions Combined treatment with suboccipital muscle inhibition and interferential current in patients with CTTH did not significantly improve self-reported pain but did reduce disability and the impact of headache on daily life at 4 weeks. These improvements exceed the minimum clinically important difference, demonstrating the clinical relevance of our findings.

TAFRO syndrome is a very rare disease, with less than 100 cases reported in the literature. It is classified as a type of idiopathic multicentric Castleman disease, but it has clinical, paraclinical, and histopathological characteristics that differentiate between TAFRO and idiopathic forms of Castleman disease not otherwise specified. However, it is a challenging exclusion diagnosis. TAFRO syndrome is characterized by systemic inflammatory involvement, often severe, which can present with kidney failure, and become a severe disease with a high mortality rate. The clinical manifestations of TAFRO can be confused with hematology malignancies or various autoimmune diseases. Although there are some reports of TAFRO syndrome associated with autoimmune compromise, there is no published consensus for the diagnosis or treatment. The case presented is a patient who meets the criteria to be classified as SLE, and with manifestations with significant clinical involvement, but with no improvement with standard treatment. It was found that the patient's systemic involvement was due to TAFRO, and that therefore the TAFRO syndrome could simulate SLE, something previously not described in the literature.

Intravenous lipid emulsions (ILEs) have been used widely for the treatment of local anesthetic (LA) poisoning and have been proposed as a treatment for intoxication by other drugs. However, the degree of evidence for this kind of therapy is not strong, as it comes mostly from clinical cases. The aim of this narrative review is to describe the proposed mechanisms of action for ILEs in poisoning by LA and other drugs and to evaluate recent studies in animals that support the recommendations for their use and the experience in humans that support the use of ILESs in both LA and other drug poisoning. For this purpose, a search was performed in the Embase, Medline and Google Scholar databases covering relevant articles over the last 10 years. In the case of AL poisoning, we recommend applying the protocols dictated by international guidelines, knowing that the degree of evidence is not very high. In poisoning by other drugs, ILEs are recommended in serious situations induced by liposoluble xenobiotics that do not respond to standard treatment.

Head and neck cancer patients represent a risk group for the development of fly larvae infestation in neoplastic wounds. This condition can accelerate the disease progression and increase its lethality due to local or systemic complications. The aim of this study was to conduct a scoping review on head and neck cancer associated with myiasis in order to answer the focal question: what are the occurrence, diagnosis, aetiology, treatment and outcomes of head and neck cancer associated with myiasis? This paper was structured based on the five-steps methodology proposed by Arksey and O’Malley (Int J Soc Res Methodol 2005;1:19-32), and followed the PRISMA Extension for Scoping Reviews (PRISMA-ScR), OSF Registries protocol. The electronic search was performed in the MEDLINE/PubMed, Embase and SciELO.org databases for articles published up to 28 February 2021. In total, 38 articles and 56 patients were included. Most patients were male (66%), and the mean age was 66.63 years. Cases were predominantly associated with squamous or basal cell cancer. The most affected anatomical sites were the eyes, scalp, ears and oral cavity, and the most frequent type of larva was Crisomyia (13%). Manual removal of the larvae was considered the standard treatment, associated or not with antibiotics, analgesics and antiparasitic drugs.

Background: Acute wrist trauma with clinical suspicion of a scaphoid fracture, but normal radiographs, is known as a clinical scaphoid fracture. Standard treatment involves immobilization and repeat radiographs in 10 to 14 days. When repeat radiographs are normal but a scaphoid fracture is still clinically suspected, the optimal management in children is unknown. This study retrospectively assessed the management and outcomes of pediatric patients diagnosed with clinical scaphoid fractures. Methods: A retrospective study was performed of all patients over a 2-year period treated for a clinical scaphoid fracture at a tertiary pediatric center. Patients were included if they had clinical signs of a scaphoid fracture and 2 negative x-rays 7 to 14 days apart postinjury. Results: Ninety-one patients with a mean age of 13.2 years (range: 7.8-17.7) were included. Sixteen patients (17.6%) underwent computed tomography (CT) or magnetic resonance imaging (MRI) at a mean time of 10.2 weeks postinjury. Five patients (5.5%) were diagnosed with a scaphoid fracture by x-ray or CT at an average of 4.5 weeks postinjury (range: 3-6). Six patients were diagnosed with other wrist fractures at a mean time postinjury of 3.1 (range: 3-6.5) weeks. Out of 195 total radiographs, the surgeon and radiologist disagreed on 59 (30.2%) images. No patients underwent surgery. Conclusions: Management of clinical scaphoid fractures at our institution was relatively uniform: nearly all patients were immobilized and less than 20% received advanced imaging. Our findings suggest a low but non-zero occult scaphoid fracture rate, discordance in radiologic interpretation, and lack of advanced imaging, providing an avenue for future prospective studies.

Background In clinical practice, standard endoscopic treatment of biliary stones fails in up to 10% of patients, and more invasive procedures such as percutaneous trans-hepatic interventions or surgery might become necessary. The aim of this multi-center retrospective study, based on prospectively-collected data, was to evaluate both the efficacy and the safety of Digital-Single Operator Cholangioscopy (D-SOC) to treat difficult biliary stones, in cases with a previous failure of conventional endoscopic methods. Methods Only patients with a previous failure of endoscopic standard treatment and a DSOC- based biliary stone treatment using electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) were included. The primary endpoint was to evaluate the stone clearance rate per procedure and per patient. Out of 1258 ERCP performed at our (three?) centers, 31 cholangioscopies in 21 patients were solely performed for the treatment of difficult biliary stones using EHL or LL. Results A complete biliary stone removal was achieved in 67.7% (21/31) of all procedures including initial and repeated examinations, while in 35.4% (11/31) of all procedures an incomplete removal was accomplished of which 36.3% had a partial stone removal. In 22 procedures EHL was adopted as techniques to fragment and remove biliary stones, while in 9 procedures LL was used. In both the techniques, the complete stone removal rate and the incomplete stone removal rate were similar (75% vs 77.7%, p>.05). Furthermore, the success rate of digital DSOC to treat difficult biliary stones was assessed per patient: overall, 100% of patients with difficult biliary stones were successfully treated using D-SOC. Only one patient experienced mild cholangitis classified ad mild adverse event following ASGE (American Society of Gastrointestinal Endoscopy) lexicon. Conclusions In conclusion, our data indicate that digital D-SOC assisted biliary stone treatment is highly efficient for the treatment of difficult biliary stones even in such patients in whom previous conventional endoscopic methods to treat biliary stones have failed. Therefore, D-SOC might be considered the new standard of care for these patients, being both, effective and safe.

Stress management interventions (SMIs) can alleviate the psychosocial stress often experienced by women with heart failure. The purpose of this meta-analysis was to summarize women's participation rates, and predictors of participation, in SMIs for the management of psychosocial distress in women with chronic HF. Studies were retrieved from bibliographic databases, reference sections of relevant papers, and research registries. Included studies (a) evaluated a SMI approach for the management of chronic HF, (b) sampled chronic HF patients, and (c) used a randomized controlled trial (RCT) design. Independent coders extracted the relevant data. Thirty-five RCTs met inclusion criteria (N = 3,649; mean age = 63.5 ± 7.0 years). All studies sampled both men and women; the mean proportion of women who participated in the trials was 38.8% (95% confidence interval [CI] = 34.5-43.4; I 2 = 82.4, 95% CI = 81.0-83.6). Women's participation rates were higher in studies sampling more HF patients with hypertension (B = 1.01, SE = 0.45, P = .046) but fewer HF patients prescribed beta blockers (B = -1.10, SE = 0.33, P = .006), F (2,12) = 6.27, P = 0.014, adjusted R 2 = 61%. SMIs may offer women a complementary or integrative approach to standard treatment to help manage the psychological distress associated with HF. Future research should explore the potential benefits of offering stress management approaches to women as part of comprehensive HF care.

Background Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse side effect of antiresorptive agents. However, withdrawal of antiresorptive agents in patients with osteoporosis may increase the risk of fractures. The treatment of MRONJ is challenging and standard treatment guidelines have yet to be established. In this study, the aim was to examined whether adjunct daily or weekly teriparatide (TPTD) injections are beneficial for the bone exposure of MRONJ lesions compared to standard conservative management. We also studied the complications and patients’ responses to TPTD therapy. Methods We enrolled 27 patients, from January 2012 until December 2016, with chronic and refractory MRONJ. There were 4 men and 23 women, with 85% of the total number being females. Nine patients who did not select TPTD therapy for several reasons formed the non-TPTD group and the remaining 18 patients were randomly assigned to the daily (n=9) or weekly (n=9) groups. All subjects in both TPTD groups continued standard conservative therapy in addition to their daily or weekly subcutaneous injection of TPTD. The daily group received a daily injection of TPTD (20 μg) and the weekly group received a weekly injection of TPTD (56.5 μg). We evaluated the complications and benefits of TPTD therapy of MRONJ. Results Three patients in the daily group did not complete the study, resulting in six patients in the daily group, nine patients in the weekly group, and nine patients in the non-TPTD group for the final analysis. Each patient in TPTD group demonstrated complete coverage of the exposed bone with normal mucosa. The TPTD group showed a shorter healing period compared to the non-TPTD group. There were no complications of atypical fractures of the femoral head in any patient. Conclusions Daily and weekly TPTD treatment resulted in a shortened treatment period compared with standard conservative therapy with no increase in the rate of complications or worsening of osteoporosis.

Background Current scientific evidence on the effect of Extracorporeal Shock Wave Therapy (ESWT) as adjunctive treatment for postburn scars is scarce. However preliminary evidence, indicates it might prove a useful tool. Materials and methods A prospective, randomized, controlled study was conducted from February 2017 to February 2019. Patients with postburn scars were divided into two groups with twenty patients per group. The control group received the standard treatment for postburn scars. The ESWT group received the standard treatment and treatment of postburn scars with ESWT 512 impulses of 0.15 mJ/mm2 in each session, twice per week for 4 weeks. We assessed the appearance of scar with the Vancouver Scar Scale (VSS), pruritus and pain with Visual Analog Scale (VAS) before the start of the treatment and at 2 weeks and 5 months after the treatment. Results Both groups showed improvements in all variables through the study. However, these improvements were only statistically significant for the VSS at the 6th month for the control group and VSS and VAS pain and pruritus for the ESWT group. Nonetheless the results failed to show statistically significant differences between the ESWT and the control group neither at two weeks after treatment nor at 5 months after treatment. Conclusion Our study questions the relevance of ESWT as adjunctive treatment for postburn scars as far as outward appearance, pain and pruritus as end-results are concern. Nonetheless, further studies are required to accurately assess the potential benefits of ESWT as an adjunctive treatment for postburn scars.

International audience; Thymic epithelial tumors are rare neoplastic proliferations of thymic epithelial cells. The aggressiveness of these malignancies increases as higher is the histologic subtype, being thymic carcinoma the most aggressive subtype, with a greater tendency to metastatic spread. In metastatic setting, there is no standard treatment after progression on platinum-based chemotherapy. In this scenario, monotherapy treatment either with lenvatinib, a multi-tyrosine kinase inhibitor with antiangiogenic properties, or pembrolizumab, an immune-checkpoint inhibitor, has reported clinical activity. Potential combination of both agents may have synergistic activity as reported in other cancer types. PECATI trial is a single-arm, investigator-initiated phase II study aiming to assess the activity and safety of the combination of lenvatinib and pembrolizumab in 43 patients with advanced B3-thymoma or thymic carcinoma who progressed on or after at least one previous line of platinum-based chemotherapy. The primary endpoint of the trial is 5-month progression-free survival rate and the secondary endpoints include overall response rate, duration of response, and overall survival.

Background: Despite recent advances in first-line chemotherapy for advanced pancreatic cancer, standard treatment after the failure of initial chemotherapy has not been established. Hence, we aimed to retrospectively analyze the clinical characteristics and outcomes of second-line chemotherapy in patients with advanced pancreatic cancer. Methods: We reviewed the clinical data of patients with advanced pancreatic cancer who underwent palliative chemotherapy at Kosin University Gospel Hospital between January 2013 and October 2020.Results: Among 366 patients with advanced pancreatic cancer who had received palliative chemotherapy, 104 (28.4%) underwent at least one cycle of second-line chemotherapy. The median age of the patients at the time of initiating second-line treatment was 62 years (interquartile range, 57–62 years), and 58.7% (61 patients) of them were male. The common second-line chemotherapy regimens were 5-fluorouracil (FU) plus leucovorin, irinotecan, and oxaliplatin (33 patients, 31.7%); gemcitabine/nab-paclitaxel (29, 27.9%), gemcitabine±erlotinib (13, 12.5%); and oxaliplatin and 5-FU/leucovorin (12, 11.5%). The median overall survival (OS) and progression-free survival were 6.4 months (95% confidence interval [CI], 4.5–8.6 months) and 4.5 months (95% CI, 2.7–6.3 months), respectively. In a multivariate analysis, poor performance status (PS) (hazard ratio [HR], 2.247; p=0.021), metastatic disease (HR, 2.745; p=0.011), and elevated carcinoembryonic antigen (CEA) levels (HR, 1.939; p=0.030) at the beginning of second-line chemotherapy were associated with poor OS.Conclusion: The survival outcome of second-line chemotherapy for advanced pancreatic cancer remains poor. However, PS, disease extent (locally advanced or metastatic), and CEA level may help determine patients who could benefit from second-line treatment.

Kampo Medicine is a traditional Japanese medicine that is well-integrated in modern medicine. Anti-cancer agents are highly developed, and evidence of standard treatment has accumulated. Kampo Medicine is needed to support patients with cancer who lose vital energy and feel cold. Cancer chemotherapy is associated with various adverse reactions, such as anorexia, general malaise/fatigue, and peripheral neuropathy, which are refractory to modern therapy. Recently, evidence of Kampo Medicines for these symptoms has been reported as randomized controlled trials (RCTs). The Japan Society for Oriental Medicine celebrated the first 20 years of the activities of evidence-based medicine (EBM) committee in June 2021. Among the activities of the EBM committee, Evidence Reports of Kampo Treatment contains RCTs and meta-analyses, including RCTs on cancer supportive care. There is accumulating evidence for the following Kampo formula for each symptom: Hangeshashinto for mucositis, rikkunshito for anorexia, goshajinkigan and ninjin'yoeito for peripheral neuropathy, hochuekkito for general malaise/fatigue, and shakuyakukanzoto for myalgia/arthralgia. However, there is insufficient evidence, and further clinical trials are needed. Supportive care with Kampo Medicine will lead to a more complete standard treatment for cancer.

BACKGROUND Non-small cell lung cancer patients with multiple high-risk socioeconomic factors experience treatment and survival disparities. We aim to assess whether disparities in treatment and survival vary by region for patients with 3 or more high-risk socioeconomic factors. METHODS The National Cancer Database was queried for patients with clinical stage I-IIA non-small cell lung cancer diagnosed between 2010 and 2015. Patients were categorized into 3 groups: standard treatment, nonstandard treatment, and no curative treatment. Multivariable logistic regression was used to evaluate regional differences in treatment. Cox proportional hazards regression and the Kaplan-Meier method were used for survival analysis. All statistical tests were 2-sided. RESULTS A total of 93,211 patients met inclusion criteria. For patients with 3 or more high-risk socioeconomic factors, the odds of nonstandard treatment were significantly greater in 6 regions compared with New England, greatest in West North Central (odds ratio 2.09, P < .001). The odds of no curative treatment were significantly greater in 7 regions compared with New England, greatest in West South Central (odds ratio 3.56, P < .001). West North Central was associated with the highest risk of all-cause mortality compared with New England (hazard ratio 1.10, P < .001), and Middle Atlantic was associated with the lowest (hazard ratio 0.86, P < .001). The 5-year overall survival was longest in Middle Atlantic (60.8%) and shortest in Mountain (36.8%). CONCLUSIONS Patients with 3 or more high-risk socioeconomic factors experience treatment and survival disparities across the United States, though disparities are more pronounced in certain regions. Regional interventions may help mitigate disparities among highest risk non-small cell lung cancer patients.

Introduction Condyloma acuminata (CA) of the urethra presents a management challenge due to high recurrence rates, difficulty in accessing urethral lesions, risk of stricture formation, and potential for sexual dysfunction. While standard treatment modalities are acceptable for some external genital condyloma, they are not always feasible or appropriate for urethral lesions. Objectives We sought to review the literature on epidemiology, presentation, diagnosis and treatment of urothelial CA with a focus on surgical treatment options. Methods We performed a comprehensive literature search of PubMed to identify all studies pertaining to urethral CA through November 2020. Results Urethral CA is a relatively rare, but challenging disease to manage with a considerable amount of treatment side effects and downstream morbidity associated. In our comprehensive review we have found a wide selection of treatment modalities ranging from minimally invasive strategies to surgical reconstructive techniques. Proper follow-up to monitor for disease recurrence at the 3–4 month mark is appropriate and will determine subsequent treatment strategies as needed. Future studies and treatment directions include novel drug delivery models to optimize minimally invasive topical drug efficacy. Conclusion Treatment of urethral CA should be approached in a step-wise fashion. Medical therapy would be an appropriate option for asymptomatic or minimally symptomatic patients with small lesions who desire to avoid any interventions. If patient is symptomatic, has extensive disease burden or has failed medical therapy intervention should be considered with options including PDT, laser ablation or surgical excision with or without urethral reconstruction. Appropriate selection depends on patient characteristics and preferences along with prior treatment history. Kim CJ, Campbell SP, Allkanjari A, et al. Update on the Medical and Surgical Management of Urethral Condyloma. Sex Med Rev 2021;xxx:xxx–xxx.

The authors report the case of a 71-year-old woman presented to the Emergency Department with acute ischemic stroke. She was treated with rt-PA and interventional endovascular revascularization and developed rapidly progressing angioedema that led to emergency intubation. The standard treatment was not very effective and the swelling improved after infusion of fresh frozen plasma. Angioedema after rt-PA infusion could be a life-threatening emergency that requires quick airway management by skilled professionals. As this condition is triggered by several factors, such as unregulated histamine and bradykinin production, the traditional treatment recommended by the guidelines may not be sufficient and the use of FFP can be considered as a safe and valuable aid.

Glioblastoma multiforme is the most common primary central nervous system tumor, with an incidence of 3 [...]

Objective Tuberculous otitis media (TB OM) is a rare disease. We present here our experience of TB OM on its clinical presentation, investigation and treatment outcome. Methods A retrospective observational study was performed and clinical data of patients in whom TB OM was diagnosed at our center between 2008 and 2019 was analyzed. Results Five cases of TB OM were identified. Otorrhoea was the most consistent presenting chief complaint while one of the cases presented with right post-auricular swelling. All the cases were successfully treated with anti-tuberculous medication with outcome of dry middle ear but only one case achieved full recovery of hearing loss. Conclusion Due to the disparity of presentations in all our patients, we would like to emphasize the high index of suspicion of TB OM in acute or chronic cases of otitis media with unusual presentation or poor response to standard treatment.

Although stomal and parastomal varices are uncommon causes of variceal bleeding, the mortality rate might be as high as 40%. Timely intervention is essential for the management of these ectopic bleeding varices. Due to the rarity of such varices, no standard treatment guideline is available. We present three cases of bleeding stomal varices managed with an endovascular approach, one through percutaneous transhepatic and the other two through transjugular intrahepatic portosystemic shunt approach.

Introduction The standard treatment for caries is to apply silver diamine fluoride (SDF) to the tooth, followed by a composite resin or glass ionomer cement restoration (GIC). Tooth discolouration is an adverse effect of SDF. The aims of this study were to 1) determine whether applying a composite compared to a GIC restoration after SDF to caries-infected teeth results in less discoloration, and 2) determine whether immediate or delayed restoration application is associated with less discoloration. Methods Sixty samples of caries-infected teeth were divided into five groups: 1) control (SDF alone), 2) SDF plus immediate composite restoration, 3) SDF plus immediate GIC restoration, 4) SDF plus delayed composite restoration, and 5) SDF plus delayed GIC restoration. The delay between SDF and restoration for groups 4 and 5 was two weeks. Tooth color was measured at three sites for each sample at baseline before SDF application and at multiple times. Results When comparing the change between baseline color to the color at the last time measurement in all groups, we found that Group 4 (17.4±4.3) and Group 5 (14.4±5.3) changed the least compared to baseline and were not statistically significantly different from each other. Conclusion Under laboratory conditions, delaying application of restoration for two weeks after SDF to samples of caries-infected teeth significantly reduced discoloration, with neither composite nor GIC being superior. If these findings are confirmed in a clinical setting, delaying restoration by two weeks could provide an inexpensive oral health strategy to reduce the negative aesthetic impact associated with SDF.

Complex distal femoral fracture (DFF) in the elderly patient is an infrequent but challenging scenario. In these fragile patients, DFF is associated with a high rate of medical complications and mortality. The optimum treatment remains controversial. Our aim is to propose our standard treatment, describe our results and discuss its clinical relevance. We describe three cases of elderly and fragile patients with multiple comorbidities who suffered a complex DFF after low energy trauma. They were successfully treated through a primary arthroplasty with distal femoral replacement (DFR). All the three patients presented early full weight-bearing mobilization (average time to first ambulation was five days), good functional outcome (mean knee range of motion was 103°) and short hospital length of stay (mean of ten days). According to our experience, primary arthroplasty with DFR could be a good therapeutic option for complex DFF in elderly patients.

Background: Combinations based on immune checkpoint inhibitors are the new first-line standard treatment for metastatic renal cell carcinoma. Sarcomatoid renal cell carcinoma (sRCC) has a dismal prognosis but good immunogenicity. Methods: The authors performed a network meta-analysis of Phase III randomized trials of immune checkpoint inhibitor-based combinations versus standard tyrosine kinase inhibitor monotherapy reporting data for sRCC. The end points were overall survival, progression-free survival and objective response rate. Results: Five trials comprising 569 sRCC patients (out of a total of 4409 metastatic renal cell carcinoma patients) were included. Nivolumab–cabozantinib was the highest ranking treatment for overall survival (p-score = 88%) and progression-free survival (p-score = 81%). Atezolizumab–bevacizumab had the highest rank for objective response rate (p-score = 80%). Conclusion: Despite some limitations, nivolumab–cabozantinib might be the preferred first-line option for sRCC in terms of efficacy.

Background: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. Patients and methods: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). Results: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8- 32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade >= 3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. Conclusions: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade >= 3 TRAEs were more common in patients on combination.

Prolonged exposure therapy (PE) has gained strong empirical support for posttraumatic stress disorder (PTSD) in the general population. However, some authors have suggested that exposure therapies may be less effective for the treatment of PTSD in older adults. There is a paucity of empirical treatment studies for older adults with PTSD. The extant studies are briefly reviewed. There are indications that exposure therapies can be feasible, safe, and efficacious for older adults. However, the degree and maintenance of gains may be reduced in older adults relative to younger adults. A case example is presented to provide a detailed illustration of PE conducted with an older adult. The treatment is presented in five phases, including standard treatment components and suggested modifications for older adults. The modifications include careful use of terminology, slowing down the presentation of some information, involvement of family members, and utilizing technology to minimize the negative effects of physical impairments and stigma.

Objectives Use of Motivational Interviewing (MI) in education may improve medication-overuse headache (MOH) patients’ ability to cope with pain. In a randomised controlled trial, we evaluated the effect of education focusing on behavioural change among MOH patients. Methods Ninety-eight MOH patients were randomized (1:1) to standard treatment and 12-weeks of MI-based education versus standard treatment alone after detoxification. Outcome of interest was changes in coping strategies measured by the Coping Strategy Questionnaire at four- and nine months. Results The educational program improved patients’ perceived efficacy in the use of their coping strategies to control pain, both at four-and nine months follow-up (mean±SE): ∆:0.84 ± 0.35, 95% CI:0.16;1.52, p = 0.02 and: ∆: 0.90 ± 0.39, 95% CI:0.14;1.66, p = 0.02, respectively. No between-group differences were detected in the other coping subscales. Within the intervention group, the coping strategy subscales Catastrophizing, and Reinterpretation of pain sensation were significantly improved at nine months follow-up (p = 0.003 vs. p = 0.012, respectively). No changes were found in the control group. Conclusion MI-based education focused on behavioural changes improved MOH patients’ perceived efficacy in the use of their coping strategies to control pain. Practice implications Education based on MI could be valuable for MOH patients with respect to behavioural changes and perceived headache control.

Introduction Cephalomedullary nailing (CMN) is the standard treatment for internal fixation of trochanteric fractures. Complications related to CMN include intraoperative fracture (IF), which is difficult to detect using only plain radiographs. However, analyses of IFs using plain radiographs and computed tomography (CT) with a large sample size of clinical cases are lacking. Therefore, this study aimed to report the incidence of IFs diagnosed by CT, the risk factors for IFs, and a comparison of clinical outcomes between patients with and without IFs. Methods This multicenter retrospective cohort study included 638 patients who underwent CMN fixation for trochanteric fractures. We evaluated IF using pre-and postoperative plain radiographs and CT. The primary outcome was reoperation and the secondary outcome was the proportion of patients who regained independent mobility at 3 months postoperatively. Furthermore, we conducted multivariable logistic regression analyses to examine the association between risk factors and IFs. Results Seventy-five (11.8%) patients had IFs, including 53 patients with occult IFs (8.3%). The most common location of IF was at the interference with the lag screw entry (45.3%). The nail insertion procedure (17.3%) was the most common reason for IF. In the assessment of clinical outcomes, patients with IFs had no reoperations and independent mobility at postoperative 3 months was lower (69.6% vs. 79.1%). Regarding regaining independent walking in the IF group, IF distal to lag screw entry and obvious IF diagnosed with plain radiographs were poor factors. The multivariable analysis showed that only inadequate reduction on the anteroposterior view based on the plain radiograph was significantly associated with the incidence of IFs (odds ratio 3.91; 95% CI, 1.28–11.94; p = 0.017). Conclusions This multicenter study indicated that the incidence of IFs detected by CT in CMN treatment for trochanteric fractures was 11.8%. An inadequate reduction in the anteroposterior view based on plain radiographs was the only independent risk factor of IFs. In the assessment of clinical outcomes, patients with IF had no incidences of reoperation. However, patients with IFs tended not to regain independent mobility compared with those without IFs.

We performed a post hoc analysis of the Belimumab International Study in Lupus Nephritis (BLISS-LN), a Phase 3, multinational, double-blind, 104-week trial, in which 448 patients with lupus nephritis were randomized to receive intravenous belimumab 10 mg/kg or placebo with standard therapy (cyclophosphamide/azathioprine or mycophenolate mofetil). Add-on belimumab was found to be most effective in improving the primary efficacy kidney response and complete kidney response in patients with proliferative lupus nephritis and a baseline urine protein/creatinine ratio under 3 g/g. However, there was no observed improvement in the kidney response with belimumab treatment in patients with lupus nephritis and sub-epithelial deposits or with a baseline protein/creatinine ratio of 3 g/g or more. Belimumab significantly reduced the risk of kidney-related events or death and lupus nephritis flare in the overall population. Belimumab reduced the risk of a sustained 30% or 40% decline in estimated glomerular filtration rate (eGFR) versus standard treatment alone and attenuated the annual rate of eGFR decline in patients who remained on-study. Thus, our data suggest that the addition of belimumab to standard therapy could attenuate the risk of lupus nephritis flare and eGFR decline in a broad spectrum of patients with lupus nephritis.