Recurrent Gallbladder Carcinoma With pMMR/MSS Achieved a Complete Response Following Camrelizumab Combined With Apatinib: A Case Report

Gallbladder carcinoma (GBC) with proficient mismatch repair (pMMR)/microsatellite stable (MSS) is associated with limited response to programmed death-1 (PD-1) inhibitor monotherapy. Limited data of PD-1 blockade combined with anti-angiogenic therapy in GBC are reported. One recurrent GBC patient with pMMR/MSS was treated with camrelizumab plus apatinib. After 4 cycles of combination therapy, the patient achieved a durable complete response with manageable toxicity. The next-generation sequencing and immunohistochemistry analysis showed that tumor mutation burden (TMB) was 7.26 mutants/Mb and PD-L1 expression was 10% (tumor proportion score) and 20% (immune proportion score). This case suggests that camrelizumab in combination with apatinib may be an effective treatment option for GBC patients with pMMR/MSS status, who have moderate expression of TMB and PD-L1. Additionally, TMB and PD-L1 expression may serve as potential biomarkers for predicting PD-1 inhibitor response of GBC. Furthermore, this needs to be verified in future studies.

Bone Sarcoma Of The Pelvis: A Multicentric Retrospective Study Of One Hundred-Fourteen Cases

Background: The aim of this study was to assess the oncologic outcome of pelvic bone sarcomas (PBS) and to identify prognosis factors.Methods: We report a multicentric cohort of patients treated for a PBS from 2000 to 2020. Data from 12 hospitals were analysed. Patients treated for primary PBS were included. Alive patients with less than 6 months of follow up were excluded. The primary outcome was survival.Results: One hundred and fourteen patients (67 males and 48 females) were reviewed with a mean follow up of 32±46,5 (1 to 216) months. The mean patient and doctor diagnosis delays were respectively 8,5±10,2 (1 to 60) and 3±4,3 (0 to 24) months. Sixty-eight patients (59,6%) died after a mean time from diagnosis of 15,9±22,8 (1 to 120) months. The overall survival rates at 5 and 10 years were respectively 38,4% and 27,6%. Chondrosarcoma histological type (HR=3,64), metastasis (HR=3,55) and surgery (HR=0,12) were identified as significant survival factors. Surgery was also associated to a decreased risk of metastasis (OR=0,03, 95% CI: 0,01 – 0,1). Among the 76 patients (66,7%) who underwent surgery, local recurrence was observed in 19 patients (25%) with a mean time from surgery to onset of 11,05 (±17,5) months. Conclusions: This nation-wide20-year-cohort study shows that surgery is the most effective treatment option in PBS regardless the histological type of the tumour. Efforts have to be done to decrease the diagnosis delay in order to start treatment when surgery is still feasible.

Challenges of CRISPR-based Gene Editing in Primary T Cells

Adaptive T cell immunotherapy holds great promise for the successful treatment of leukemia as well as other types of cancers. More recently, it was also shown to be an effective treatment option for chronic virus infections in immunosuppressed patients. Autologous or allogeneic T cells used for immunotherapy are usually genetically modified to express novel T cell or chimeric antigen receptors. The production of such cells was significantly simplified with the CRISPR/Cas system allowing deletion or insertion of novel genes at specific locations within the genome. In this review, we describe recent methodological breakthroughs important for the conduction of these genetic modifications, summarize crucial points to be considered when conducting such experiments, and highlight the potential pitfalls of these approaches.

Reflux, Barrett’s Esophagus, and Esophageal Adenocarcinoma After Bariatric Surgery

We present the case of a patient who developed esophageal adenocarcinoma after a previous laparoscopic sleeve gastrectomy. Bariatric surgery has emerged as the most effective treatment option for weight loss and obesity-related diseases; however, sleeve gastrectomy promotes gastroesophageal reflux and leads to Barrett’s esophagus in a substantial portion of patients. The natural history of Barrett’s esophagus in these patients is unknown, and active surveillance is recommended until the incidence of dysplasia and adenocarcinoma in this population is clarified. Management options for these patients include conversion to Roux-en-Y gastric bypass. Although esophagectomy in patients who have previously undergone sleeve gastrectomy may require an alternative conduit, the remnant stomach can be used in carefully selected patients. Here, we review the different weight loss procedures, their effect on gastroesophageal reflux disease and Barrett’s esophagus, and the treatment options for patients with esophageal cancer after sleeve gastrectomy. We report the use of preoperative coil embolization as a means of vascular preconditioning before successful use of a gastric conduit.

The Cost-Effectiveness of Supplemental Carnosine in Type 2 Diabetes

In this paper, we assess the cost-effectiveness of 1 g daily of carnosine (an over the counter supplement) in addition to standard care for the management of type 2 diabetes and compare it to standard care alone. Dynamic multistate life table models were constructed in order to estimate both clinical outcomes and costs of Australians aged 18 years and above with and without type 2 diabetes over a ten-year period, 2020 to 2029. The dynamic nature of the model allowed for population change over time (migration and deaths) and accounted for the development of new cases of diabetes. The three health states were ‘Alive without type 2 diabetes’, ‘Alive with type 2 diabetes’ and ‘Dead’. Transition probabilities, costs, and utilities were obtained from published sources. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. Over the ten-year period, the addition of carnosine to standard care treatment resulted in ICERs (discounted) of AUD 34,836 per YoLS and AUD 43,270 per QALY gained. Assuming the commonly accepted willingness to pay threshold of AUD 50,000 per QALY gained, supplemental dietary carnosine may be a cost-effective treatment option for people with type 2 diabetes in Australia.

Can Digital Therapeutics Open a New Era of Sleep Medicine?

Digital therapeutics (DTx) are products that provide evidence-based interventions driven by high-quality software programs to prevent, manage, or treat a medical disease. DTx are receiving increasing attention as a new therapeutic approach. Several DTx for insomnia are on the market, some of which have received approval by national regulatory agencies. DTx for insomnia are usually based on cognitive behavioral therapy for insomnia. No DTx for other sleep disorders, such as narcolepsy or sleep-related breathing disorders, have received regulatory authority approval as a medical device. DTx have the substantial benefits of being accessible and relatively low-cost. However, several issues related to DTx have not yet been fully resolved, and discussions regarding DTx are still in the early stages. To use DTx for sleep disorders as an effective treatment option in the future, considering the current status of DTx is necessary. This review discusses definitions and background of DTx; specific DTx for insomnia that have been developed; use of DTx for sleep and related psychiatric comorbid symptoms; global regulatory processes for DTx, including prescribing and medical billing issues; and remaining challenges regarding the use of DTx.

5-HT3 Antagonist for Pregnancy Associated Nausea and Vomiting

5-HT3 antagonists appear to be an effective treatment option in the treatment of nausea and vomiting associated with pregnancy. Literature suggests an increased risk of congenital defects in fetuses exposed to ondansetron during pregnancy, especially during first trimester. Health authorities now suggest that this drug should not be used during this period. However, this decision is debatable and whether ondansetron can be used in pregnant women is still controversial.

Long-Term Outcomes Following Manipulation Under Anaesthetic for Patients with Primary and Secondary Frozen ShoulderShoulder

Background Frozen Shoulder (FS) is a common, debilitating condition for which manipulation under anaesthetic (MUA) is a non-invasive and effective treatment option. Current literature evaluates short to medium-term outcomes, but there is a paucity of long-term (>10 years) studies. Knowledge of long-term outcomes is also needed to evaluate whether FS or its treatment pre-disposes to other shoulder pathology in the long-term. Methods A retrospective analysis of 398 shoulders undergoing MUA for FS between Jan 1999 and Jan 2010; 240 complete datasets were obtained. Outcomes were Oxford Shoulder Score (OSS), recurrence and development of other shoulder pathology (arthritis or rotator cuff tear). Results At long-term follow-up (mean 13.2 years), 71.3% had no symptoms (OSS 48), 16.6% had minor symptoms (OSS 42–47) and 12.1% had significant symptoms (OSS < 42). There were 4/240 (1.7%) self-reported recurrences > 5 years after initial MUA and 2/240 (0.8%) repeat MUAs. In the long-term 6.7% developed rotator cuff pathology and 3.8% shoulder OA. Discussion This study suggests that long-term outcome after MUA for FS is favourable. Late recurrence of FS is uncommon and the development of OA or rotator cuff pathology is no greater than that of the general population.

Assessment of patient satisfaction after levonorgestral containing intrauterine system insertion in women with abnormal uterine bleeding

Background: Abnormal uterine bleeding is a common gynecological complaint affecting 10-30% of reproductive-aged women and it can result from different causes which adversely affects the woman’s quality of life, necessitating its appropriate and adequate management. Among all the pharmacological and surgical management options of AUB. LNG-IUS is emerging as a safer and effective treatment option of AUB. However apprehension about discomfort associated with the use of intrauterine device leads to its untimely removal. Aim of current study was to conduct a prospective qualitative study to observe the level of patient satisfaction with the use of LNG-IUS in patients with abnormal uterine bleeding.Methods: This study was conducted in the department of obstetrics and gynecology, MGM medical college and M.Y. Group of Hospitals, Indore from March 2017- March 2018. Follow up was done at 1, 3, 6 months.Results: In our study, majority of the women (90%) had improvement in their abnormal uterine bleeding along with significant increase in mean hemoglobin level from7.30+1.29 gm% to 8.71+1.27 gm% at the end of six months. 86.66% of these patients were very satisfied with the use of LNG IUS,Conclusions: LNG-IUS is an effective device for medical management of AUB and it should be used as the first line therapy for the same. It should always be considered before surgical interventions. It yields promising result in terms of patient satisfaction.

Proximal Interphalangeal Joint Arthroplasty Using the Wide-Awake Local Anesthesia No Tourniquet Technique

Background: Proximal interphalangeal joint (PIPJ) osteoarthritis is a common condition that results in pain, stiffness, and loss of function in the affected hand. Proximal interphalangeal joint arthroplasty is an effective treatment option when conservative methods have failed. The wide-awake local anesthesia no tourniquet (WALANT) technique to perform surgery carries advantages such as lack of tourniquet discomfort, reduces the staffing and costs associated with anesthesia and sedation, and allows faster recovery. We aimed to determine whether the WALANT technique was safe and effective in the context of PIPJ arthroplasty. Methods: Patients were enrolled retrospectively from January 2015 to October 2020 by examining operating theater records and surgeon logbooks. Electronic patient records were examined to obtain patient data. Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaires and Visual Analog Scale (VAS) for pain were sent by post to patients—with a separate DASH and VAS for each digit operated on. Results: Twenty-nine PIPJ arthroplasties were carried out using WALANT technique by 3 different surgeons all using the dorsal approach. All cases were successfully carried out as day-case procedures. There was a significant correlation with increasing VAS and increasing DASH score. Proximal interphalangeal joint arthroplasty improved range of motion from 28.9 ± 5.5° to 79.4 ± 13.3° ( P < .0001). Two cases developed complications related to surgery. Conclusions: Our study is the first to report the use of WALANT to perform PIPJ arthroplasty, and shows comparable results with traditional methods. Larger, multicenter prospective trials are required to determine the efficacy of this technique and to quantify its economical benefit.