Background: s/Aims: Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezo-bev remains unknown. Methods: In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging. Results: Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age, 58.5 years; women, 17%; Barcelona Clinic Liver Cancer stage system B/C, 5/7) had received 3-12 cycles of atezo- bev, and four of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 days (range, 54-114) following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 months (range, 4-30), none of the alive patients developed HCC recurrence or graft rejection. Conclusions Surgical therapy, including LT, is possible after atezo-bev therapy in well-selected patients after downstaging.

Introduction: COVID-19 has had a significant impact on the entire health system. The trauma and orthopaedic service has been compelled to alter working practices to respond proactively and definitively to the crisis. The aim of this study is to summarise the impact of this outbreak on the trauma and orthopaedic workload and outline the response of the department. Materials and Methods: We retrospectively collected data comparing patient numbers pre-COVID-19, and prospectively during the early COVID-19 pandemic. We have collected the numbers and nature of outpatient orthopaedic attendances to fracture clinics and elective services, inpatient admissions and the number of fracture neck of femur operations performed. Results: The number of outpatient attendances for a musculoskeletal complaint to Accident and Emergency and the number of virtual fracture clinic reviews reduced by almost 50% during COVID-19. The number of face-to-face fracture clinic follow-ups decreased by around 67%, with a five-fold increase in telephone consultations. Inpatient admissions decreased by 33%, but the average number of fracture neck of femur operations performed has increased by 20% during COVID-19 compared to pre-COVID-19 levels. Conclusion: We have noted a decrease in some aspects of the trauma and orthopaedic outpatient workload, such as leisure and occupational-related injuries but an increase in others, such as fracture neck of femurs. Many injuries have significantly reduced in numbers and we consider that a model could be developed for treating these injuries away from the acute hospital site entirely, thereby allowing the acute team to focus more appropriate major trauma injuries.

In our previous studies, we have demonstrated the association of certain variants of the thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (TG) genes with congenital hypothyroidism. Herein, we explored the mechanistic basis for this association using different in silico tools. The mRNA 3'-untranslated region (3'-UTR) plays key roles in gene expression at the post-transcriptional level. In TSHR variants (rs2268477, rs7144481, and rs17630128), the binding affinity of microRNAs (miRs) (hsa-miR-154-5p, hsa-miR-376a-2-5p, hsa-miR-3935, hsa-miR-4280, and hsa-miR-6858-3p) to the 3'-UTR is disrupted, affecting post-transcriptional gene regulation. TPO and TG are the two key proteins necessary for the biosynthesis of thyroid hormones in the presence of iodide and H2O2. Reduced stability of these proteins leads to aberrant biosynthesis of thyroid hormones. Compared to the wild-type TPO protein, the p.S398T variant was found to exhibit less stability and significant rearrangements of intra-atomic bonds affecting the stoichiometry and substrate binding (binding energies, ΔG of wild-type vs. mutant: ‒15 vs. ‒13.8 kcal/mol; and dissociation constant, Kd of wild-type vs. mutant: 7.2E-12 vs. 7.0E-11 M). The missense mutations p.G653D and p.R1999W on the TG protein showed altered ΔG (0.24 kcal/mol and 0.79 kcal/mol, respectively). In conclusion, an in silico analysis of TSHR genetic variants in the 3'-UTR showed that they alter the binding affinities of different miRs. The TPO protein structure and mutant protein complex (p.S398T) are less stable, with potentially deleterious effects. A structural and energy analysis showed that TG mutations (p.G653D and p.R1999W) reduce the stability of the TG protein and affect its structure-functional relationship.

Renal cell carcinoma (RCC) commonly metastasizes to the lung, liver, bones, and brain; however, cutaneous metastases remain rare with few reported cases. Since RCCs have the propensity to metastasize to highly vascular areas, the scalp and skin of the head and neck region are likely locations for cutaneous metastases. We report a rare case of a large, exophytic, cauliflower-like, hemorrhagic, metastatic mass of the posterior neck. This is the first reported case of a head and neck cutaneous RCC metastasis treated with endovascular embolization prior to surgical resection. Due to the increased vascularity of RCCs and risk of excessive hemorrhage during resection, adjunctive embolization of cutaneous head and neck metastasis may have a role. Essential characteristics to our treatment strategy are discussed with a review of pertinent literature.

The abscopal effect is a term that has been used to describe the phenomenon in which localized radiation therapy treatment of a tumor lesion triggers a spontaneous regression of metastatic lesion(s) at a non-irradiated distant site(s). Radiation therapy induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. However, due to the brain’s distinctive immune microenvironment, extracranial abscopal responses following cranial radiation therapy have rarely been reported. In this report, we describe the case of 42-year-old female patient with metastatic melanoma who experienced an abscopal response following her cranial radiation therapy for her brain metastasis. The patient initially presented with a stage III melanoma of the right upper skin of her back. Approximately 5 years after her diagnosis, the patient developed a large metastatic lesion in her upper right pectoral region of her chest wall and axilla. Since the patient’s tumor was positive for BRAF and MEK, targeted therapy with dabrafenib and trametinib was initiated. However, the patient experienced central nervous system (CNS) symptoms such as headache and disequilibrium and developed brain metastases prior to the start of targeted therapy. The patient received radiation therapy to a dose of 30 Gy delivered in 15 fractions to her brain lesions while the patient was on dabrafenib and trametinib therapy. The patient’s CNS metastases improved significantly within weeks of her therapy. The patient’s non-irradiated large extracranial chest mass and axilla mass also shrank substantially demonstrating the abscopal effect during her CNS radiation therapy. Following radiation therapy of her residual chest lesions, the patient was disease free clinically and her CNS lesions had regressed. However, when the radiation therapy ended and the patient continued her targeted therapy alone, recurrence outside of her previously treated fields was noted. The disease recurrence could be due to the possibility of developing BRAF resistance clones to the BRAF targeted therapy. The patient died eventually due to wide spread systemic disease recurrence despite targeted therapy.
Adult ; Axilla ; Brain ; Central Nervous System ; Clone Cells ; Diagnosis ; Female ; Headache ; Humans ; Immune System ; Immunization ; Melanoma ; Molecular Targeted Therapy ; Neoplasm Metastasis ; Radiation, Ionizing ; Recurrence ; Skin ; Skin Neoplasms ; Thoracic Wall ; Thorax

Ischemic priapism is a urological emergency that has been associated with long-standing and irreversible adverse effects on erectile function. Studies have demonstrated a linear relationship between the duration of critically ischemic episodes and the subsequent development of corporal fibrosis and irreversible erectile function loss. Placement of a penile prosthesis is a well-established therapeutic option for the management of erectile dysfunction secondary to ischemic priapism, and will be the focus of this review. Review of the current literature demonstrates a growing utilization of penile prostheses in the treatment of erectile dysfunction secondary to ischemic priapism. Unfortunately, there is a paucity of randomized-controlled trials describing the use of prosthesis in ischemic priapism. As a result, there is a lack of consensus regarding the type of prosthesis (malleable vs. inflatable), timing of surgery (acute vs. delayed), and anticipated complications for each approach. Both types of prostheses yielded comparable complication rates, but the inflatable penile prosthesis have higher satisfaction rates. Acute treatment of priapism was associated with increased risk of prosthetic infection, and could potentially cause psychological trauma, whereas delayed implantation was associated with greater corporal fibrosis, loss of penile length, and increased technical difficulty of implantation. The paucity of high-level evidence fuels the ongoing discussion of optimal use and timing of penile prosthesis implantation. Current guidance is based on consensus expert opinion derived from small, retrospective studies. Until more robust data is available, a patient-centered approach and joint decision-making between the patient and his urologist is recommended.
Consensus ; Emergencies ; Erectile Dysfunction ; Expert Testimony ; Fibrosis ; Humans ; Joints ; Male ; Penile Implantation ; Penile Prosthesis ; Priapism ; Prostheses and Implants ; Psychological Trauma ; Retrospective Studies

Rho iso-alpha acids-rich extract (RIAA) from Humulus lupulus (hops) and proanthocyanidins-rich extracts (PAC) from Acacia nilotica exert anti-inflammatory and anti-diabetic activity in vitro and in vivo. We hypothesized that a combination of these two extracts would exert enhanced effects in vitro on inflammatory markers and insulin signaling, and on nonfasting glucose and insulin in db/db mice. Over 49 tested combinations, RIAA:PAC at 5:1 (6.25 microg/mL) exhibited the greatest reductions in TNFalpha-stimulated lipolysis and IL-6 release in 3T3-L1 adipocytes, comparable to 5 microg/mL troglitazone. Pretreatment of 3T3-L1 adipocytes with this combination (5 microg/mL) also led to a 3-fold increase in insulin-stimulated glucose uptake that was comparable to 5 microg/mL pioglitazone or 901 microg/mL aspirin. Finally, db/db mice fed with RIAA:PAC at 5:1 (100 mg/kg) for 7 days resulted in 22% decrease in nonfasting glucose and 19% decrease in insulin that was comparable to 0.5 mg/kg rosiglitazone and better than 100 mg/kg metformin. RIAA:PAC mixture may have the potential to be an alternative when conventional therapy is undesirable or ineffective, and future research exploring its long-term clinical application is warranted.
Acacia ; Adipocytes ; Animals ; Aspirin ; Chromans ; Glucose ; Humulus ; Insulin ; Insulin Resistance ; Interleukin-6 ; Lipolysis ; Metformin ; Mice ; Thiazolidinediones

Orthodontic elastic bands are an important iatrogenic etiologic factor in the causation of periodontal attachment apparatus breakdown. Appropriate diagnosis and a well constructed treatment plan tailor-made to suit the requirements of the particular patient is imperative for management of periodontal lesions induced by subgingival retention of rubber band. There are conflicting reports regarding the reattachment and regeneration of lost periodontal supporting tissues in such cases. The present case report highlights the spontaneous reversal and correction of periodontal destruction due to iatrogenic orthodontic elastic band displacement deep into the subgingival tissues.

BACKGROUND/AIMS: High-resolution manometry (HRM) with pressure topography is used to subtype achalasia cardia, which has therapeutic implications. The aim of this study was to compare the clinical characteristics, manometric variables and treatment outcomes among the achalasia subtypes based on the HRM findings. METHODS: The patients who underwent HRM at the Asian Institute of Gastroenterology, Hyderabad between January 2008 and January 2009 were enrolled. The patients with achalasia were categorized into 3 subtypes: type I - achalasia with minimum esophageal pressurization, type II - achalasia with esophageal compression and type III - achalasia with spasm. The clinical and manometric variables and treatment outcomes were compared. RESULTS: Eighty-nine out of the 900 patients who underwent HRM were diagnosed as achalasia cardia. Fifty-one patients with a minimum follow-up period of 6 months were included. Types I and II achalasia were diagnosed in 24 patients each and 3 patients were diagnosed as type III achalasia. Dysphagia and regurgitation were the main presenting symptoms in patients with types I and II achalasia. Patients with type III achalasia had high basal lower esophageal sphincter pressure and maximal esophageal pressurization when compared to types I and II. Most patients underwent pneumatic dilatation (type I, 22/24; type II, 20/24; type III, 3/3). Patients with type II had the best response to pneumatic dilatation (18/20, 90.0%) compared to types I (14/22, 63.3%) and III (1/3, 33.3%). CONCLUSIONS: The type II achalasia cardia showed the best response to pneumatic dilatation.
Asian Continental Ancestry Group ; Cardia ; Deglutition Disorders ; Dilatation ; Esophageal Achalasia ; Esophageal Motility Disorders ; Esophageal Sphincter, Lower ; Follow-Up Studies ; Gastroenterology ; Humans ; Manometry ; Spasm