Low back pain is a widespread and poorly understood condition that is frequently diagnosed as non-specific low back pain. We were intrigued by the presence of painful sacroiliac nodules in patients ...with this condition. We conducted a historical review to elucidate this relationship. This chronicled review summarizes the overlooked literature from different countries, especially from around the 1950s, regarding the diagnosis and management of these painful nodules. Biopsies have confirmed the adipose nature of these nodules and revealed distinct pathological signs, including oedema and fascial fatty herniation. Studies have suggested both intra-nodule local anaesthetic injection and surgery as successful treatments for managing pain on a short- or long-term basis. Recent ultrasound studies have confirmed these findings. The various terms used for these nodules over time are specifically described. We conclude that it may be necessary to reconsider the role of fatty tissue in the aetiology and treatment of low back pain in today’s mainstream medicine. This could lead to advances in understanding unexplained musculoskeletal pain disorders beyond low back pain. Meanwhile, despite the remaining questions, the treatments identified in these studies can help physicians manage patients’ unresolved pain. We recommend that future research use this review as a foundation for further study.
Background: Despite impressive progression-free survival (PFS) results from PARP inhibitors (PARPi) in ovarian cancer, concerns about their effect on post-progression treatment outcomes have recently ...arisen, particularly when administered in the relapsed setting. Overlapping mechanisms of resistance between PARPi and platinum have been described, and optimal therapies upon progression to PARPi are unknown. We communicate real-world data (RWD) on outcomes of subsequent chemotherapy upon progression to PARPi used as maintenance in ovarian cancer relapses, particularly focusing on platinum rechallenge, according to BRCA status. Methods: Data from high-grade serous or endometrioid ovarian cancer patients who received subsequent chemotherapy after progression to maintenance PARPi in the relapsed setting, in 16 Catalan hospitals between August 2016 and April 2021, and who were followed-up until July 2021, were included. Endpoints were overall response rate (ORR), and PFS and overall survival (OS) measured from the subsequent chemotherapy starting date. Results: 111 patients were included 46 (41.4%) presented pathological BRCA1/2 mutations, 8 (7.5%) in other homologous recombination-related genes. Sixty-four patients (57.7%) had received two prior chemotherapy lines, including the one immediately prior to PARPi. PARPi were niraparib (n = 60, 54.1%), olaparib (n = 49, 44.1%), and rucaparib (n = 2, 1.8%). A total of 81 patients remained platinum-sensitive (PS population) after progression to PARPi (when progression-free interval PFI was >6 months after the last cycle of prior platinum) median PFI 12.0 months (interquartile range, IQR, 8.8−17.1). Of those, 74 were treated with subsequent platinum regimens, with the following results: ORR of 41.9%, median PFS (mPFS) of 6.6 months (95% CI 6−9.2), and median OS (mOS) of 20.6 months (95% CI 13.6−28.9). Analysis of these 74 patients according to BRCA status showed that PFIs for BRCA mutant and non BRCA-mutant patients were 13.6 IQR11.2−22.2 and 10.3 IQR 7.4−14.9 months, respectively (p = 0.010); ORR were 40.0% versus 43.6%, respectively; Rates of progression (as best response) to subsequent platinum were 45.7% versus 17.9%, respectively (p = 0.004); mPFS and mOS were 3.5 (95% CI 2.5−8.6) versus 7.5 months (95% CI 6.5−10.1, p = 0.03), and 16.4 (95% CI 9.3−27.5) versus 24.2 months (95% CI 17.2−NR, p = 0.036), respectively. Conclusion: This is the largest series of real-world data on ovarian cancer patients retreated with platinum in the post-PARPi scenario, separately analyzing BRCA mutant and non-mutant patients, to our knowledge. In our platinum-sensitive population, rechallenge with platinum after progression upon PARPi in the 3rd or later lines for ovarian cancer relapses shows relevant ORR and similar PFS outcomes to historical series of the prePARPi era. However, BRCA mutant patients presented significantly higher rates of progression under subsequent platinum and worse survival outcomes associated with subsequent platinum than non-BRCA-mutant patients.
To evaluate the prevalence of transmitted drug resistance (TDR) and non-B subtypes in patients with acute/recent HIV-1 infection in Barcelona during the period 1997-2012.
Patients from the "Hospital ...Clínic Primary HIV-1 Infection Cohort" with a genotyping test performed within 180 days of infection were included. The 2009 WHO List of Mutations for Surveillance of Transmitted HIV-1 Drug Resistance was used for estimating the prevalence of TDR and phylogenetic analysis for subtype determination.
189 patients with acute/recent HIV-1 infection were analyzed in 4 time periods (1997-2000, n=28; 2001-4, n=42; 2005-8, n=55 and 2009-12, n=64). The proportion of patients with acute/recent HIV-1 infection with respect to the total of newly HIV-diagnosed patients in our center increased over the time and was 2.18%, 3.82%, 4.15% and 4.55% for the 4 periods, respectively (p=0.005). The global prevalence of TDR was 9%, or 17.9%, 9.5%, 3.6% and 9.4% by study period (p=0.2). The increase in the last period was driven by protease-inhibitor and nucleoside-reverse-transcriptase-inhibitor resistance mutations while non-nucleoside-reverse-transcriptase inhibitor TDR and TDR of more than one family decreased. The overall prevalence of non-B subtypes was 11.1%, or 0%, 4.8%, 9.1% and 20.3 by study period (p=0.01). B/F recombinants, B/G recombinants and subtype F emerged in the last period. We also noticed an increase in the number of immigrant patients (p=0.052). The proportion of men-who-have-sex-with-men (MSM) among patients with acute/recent HIV-1 infection increased over the time (p=0.04).
The overall prevalence of TDR in patients with acute/recent HIV-1 infection in Barcelona was 9%, and it has stayed relatively stable in recent years. Non-B subtypes and immigrants proportions progressively increased.
Abstract Effective cytotoxic treatment options for advanced cervical cancer are exceedingly limited. Cisplatin-based combination chemotherapy, the most commonly used cytotoxic therapy, has produced ...response rates ranging from 20% to 30% and overall survival of less than 10 months. Because of the minimal degree of success with cytotoxic therapies and the poor prognosis of patients with this disease, interest has increased in targeted therapeutics for the treatment of cervical cancer. In recent years, significant improvements in our understanding of the altered molecular events in tumor cells have led to the discovery of new targets and agents for clinical testing. Two of these promising targets are epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) signaling pathway, which play critical roles in tumor growth and angiogenesis. Two monoclonal antibodies, cetuximab, which targets EGFR, and bevacizumab, which target the VEGF signaling pathway, are being evaluated as monotherapy and in combination with other agents and/or radiotherapy for the treatment of cervical cancer. In addition, VEGF receptor tyrosine kinase inhibitors, such as sorafenib and pazopanib, are being studied in phase I/II clinical trials. In this review, we discuss potential molecular targets and novel therapeutic strategies that are being investigated for the treatment of cervical cancer.
To examine potential markers of clinical benefit and the effects of erlotinib on the epidermal growth factor receptor (EGFR) signaling pathway in advanced non-small cell lung cancer patients ...refractory to platinum-based chemotherapy.
Patients were given erlotinib (150 mg/d). Tumor biopsies were done immediately before treatment and in a subgroup of patients after 6 weeks' treatment.
Of 73 evaluable patients, 7 (10%) had partial response and 28 (38%) had stable disease. In 53 patients with baseline tumor samples, no relationship was observed between pretreatment levels of EGFR, phosphorylated (p)-EGFR, p-AKT, p-mitogen-activated protein kinase (MAPK), or p27 and clinical benefit (i.e., response, or stable disease >/=12 weeks). Tumors from 15 of 57 patients had high EGFR gene copy number, assessed using fluorescence in situ hybridization (FISH positive), 10 of whom had clinical benefit, compared with 5 of 42 FISH-negative patients. FISH-positive patients had longer median progression-free 137 versus 43 days, P = 0.002; hazard ratio (HR), 0.37 and overall (226 versus 106 days, P = 0.267; HR, 0.70) survival than FISH-negative patients. In paired biopsy samples from 14 patients, p-EGFR (P = 0.002), p-MAPK (P = 0.001), and Ki-67 (P = 0.025) levels were significantly reduced after 6 weeks' treatment. Apoptosis was significantly increased in patients with clinical benefit (P = 0.029), and may be a marker of clinical benefit.
In this study, EGFR FISH-positive status was associated with improved outcome after erlotinib therapy. Erlotinib led to reduced levels of p-EGFR, p-MAPK, and Ki-67, and stimulated apoptosis in tumor samples from patients with clinical benefit.
Non-small-cell lung cancer (NSCLC) has experienced several diagnostic and therapeutic changes over the past two decades. However, there are few studies conducted with real-world data regarding the ...evolution of the cost of these new drugs and the corresponding changes in the survival of these patients. We collected data on patients diagnosed with NSCLC from the tumor registry of the University Hospital of Vic from 2002 to 2021. We analyzed the epidemiological and pathological characteristics of these patients, the diverse oncological treatments administered, and the survival outcomes extending at least 18 months post-diagnosis. We also collected data on pharmacological costs, aligning them with the treatments received by each patient to determine the cost associated with individualized treatments. Our study included 905 patients diagnosed with NSCLC. We observed a dynamic shift in histopathological subtypes from squamous carcinoma in the initial years to adenocarcinoma. Regarding the treatment approach, the use of chemotherapy declined over time, replaced by immunotherapy, while molecular therapy showed relative stability. An increase in survival at 18 months after diagnosis was observed in patients with advanced stages over the most recent years of this study, along with the advent of immunotherapy. Mean treatment costs per patient ranged from EUR 1413.16 to EUR 22,029.87 and reached a peak of EUR 48,283.80 in 2017 after the advent of immunotherapy. This retrospective study, based on real-world data, documents the evolution of pathological characteristics, survival rates, and medical treatment costs for NSCLC over the last two decades. After the introduction of immunotherapy, patients in advanced stages showed an improvement in survival at 18 months, coupled with an increase in treatment costs.
Although several molecular players have been described that play a role during the early phases of lung development, it is still unknown how the vasculature develops in relation to the airways. Two ...opposing models describe development of lung vasculature: one suggests that both vasculogenesis and angiogenesis are involved, whereas the second describes vasculogenesis as the primary mechanism. Therefore, we examined the development of the murine pulmonary vasculature through a morphological analysis from the onset of lung development 9.5 days postcoital (dpc) until the pseudoglandular stage (13.5 dpc). We analyzed fetal lungs of Tie2-LacZ transgenic mice as well as serial sections of wild-type lungs stained with endothelial-specific antibodies (Flk-1, Fli-1, and PECAM-1). Embryos were processed with intact blood circulation to maintain the integrity of the vasculature; hence individual vessels could be identified with accuracy through serial section analysis. Furthermore, circulating primitive erythrocytes, formed exclusively by the blood islands in the yolk sac, are trapped in vessels during fixation, which proves the connection with the embryonic circulation. We report that from the first morphological sign of lung development, a clear vascular network exists that is in contact with the embryonic circulation. We propose distal angiogenesis as a new concept for early pulmonary vascular morphogenesis. In this model, capillary networks surround the terminal buds and expand by formation of new capillaries from preexisting vessels as the lung bud grows. The fact that at an early embryonic stage a complete vascular network exists may be important for the general understanding of embryonic development.
OBJECTIVES: To evaluate the prevalence of transmitted drug
resistance (TDR) and non-B subtypes in patients with
acute/recent HIV-1 infection in Barcelona during the period
1997-2012. METHODS: ...Patients from the "Hospital Clinic Primary
HIV-1 Infection Cohort" with a genotyping test performed within
180 days of infection were included. The 2009 WHO List of
Mutations for Surveillance of Transmitted HIV-1 Drug Resistance
was used for estimating the prevalence of TDR and phylogenetic
analysis for subtype determination. RESULTS: 189 patients with
acute/recent HIV-1 infection were analyzed in 4 time periods
(1997-2000, n=28; 2001-4, n=42; 2005-8, n=55 and 2009-12, n=64).
The proportion of patients with acute/recent HIV-1 infection
with respect to the total of newly HIV-diagnosed patients in our
center increased over the time and was 2.18%, 3.82%, 4.15% and
4.55% for the 4 periods, respectively (p=0.005). The global
prevalence of TDR was 9%, or 17.9%, 9.5%, 3.6% and 9.4% by study
period (p=0.2). The increase in the last period was driven by
protease-inhibitor and
nucleoside-reverse-transcriptase-inhibitor resistance mutations
while non-nucleoside-reverse-transcriptase inhibitor TDR and TDR
of more than one family decreased. The overall prevalence of
non-B subtypes was 11.1%, or 0%, 4.8%, 9.1% and 20.3 by study
period (p=0.01). B/F recombinants, B/G recombinants and subtype
F emerged in the last period. We also noticed an increase in the
number of immigrant patients (p=0.052). The proportion of
men-who-have-sex-with-men (MSM) among patients with acute/recent
HIV-1 infection increased over the time (p=0.04). CONCLUSIONS:
The overall prevalence of TDR in patients with acute/recent
HIV-1 infection in Barcelona was 9%, and it has stayed
relatively stable in recent years. Non-B subtypes and immigrants
proportions progressively increased.
OBJECTIVES: To evaluate the prevalence of transmitted drug
resistance (TDR) and non-B subtypes in patients with
acute/recent HIV-1 infection in Barcelona during the period
1997-2012. METHODS: ...Patients from the "Hospital Clinic Primary
HIV-1 Infection Cohort" with a genotyping test performed within
180 days of infection were included. The 2009 WHO List of
Mutations for Surveillance of Transmitted HIV-1 Drug Resistance
was used for estimating the prevalence of TDR and phylogenetic
analysis for subtype determination. RESULTS: 189 patients with
acute/recent HIV-1 infection were analyzed in 4 time periods
(1997-2000, n=28; 2001-4, n=42; 2005-8, n=55 and 2009-12, n=64).
The proportion of patients with acute/recent HIV-1 infection
with respect to the total of newly HIV-diagnosed patients in our
center increased over the time and was 2.18%, 3.82%, 4.15% and
4.55% for the 4 periods, respectively (p=0.005). The global
prevalence of TDR was 9%, or 17.9%, 9.5%, 3.6% and 9.4% by study
period (p=0.2). The increase in the last period was driven by
protease-inhibitor and
nucleoside-reverse-transcriptase-inhibitor resistance mutations
while non-nucleoside-reverse-transcriptase inhibitor TDR and TDR
of more than one family decreased. The overall prevalence of
non-B subtypes was 11.1%, or 0%, 4.8%, 9.1% and 20.3 by study
period (p=0.01). B/F recombinants, B/G recombinants and subtype
F emerged in the last period. We also noticed an increase in the
number of immigrant patients (p=0.052). The proportion of
men-who-have-sex-with-men (MSM) among patients with acute/recent
HIV-1 infection increased over the time (p=0.04). CONCLUSIONS:
The overall prevalence of TDR in patients with acute/recent
HIV-1 infection in Barcelona was 9%, and it has stayed
relatively stable in recent years. Non-B subtypes and immigrants
proportions progressively increased.
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