Losing weight before IVF may increase chance of pregnancy: Study

A systematic review and meta-analysis of randomized controlled trials (RCTs) assessed whether weight loss interventions before in vitro fertilization (IVF) improved reproductive outcomes. The review found that weight loss interventions before IVF could increase the chances of pregnancy, especially in unassisted conception, although the effect on live births was unclear. The findings are published in Annals of Internal Medicine.

Researchers from the University of Oxford reviewed 12 RCTs comprising 1,921 patients conducted between 1980 through 27 of May 2025. Inclusion criteria included studies conducted on women at least 18 years old with a BMI of 27 kg/m2 or greater who were seeking IVF with or without intracytoplasmic sperm injection treatment for infertility. Outcomes of interest were number of participants achieving pregnancy without IVF (unassisted pregnancy), with IVF (treatment-induced pregnancy), overall (unassisted plus treatment-induced) and those delivering a live infant.

The researchers found that participants were typically women in their early 30s with a median baseline BMI of 33.6 kg/m2. Weight loss interventions studied included low-energy diets, an exercise program accompanied by healthy eating advice, and pharmacotherapy accompanied by diet and physical activity advice. Overall, weight loss interventions before IVF were associated with greater unassisted pregnancy rates. Evidence was inconclusive on the effect of weight loss interventions on treatment-induced pregnancies. Evidence on the association between weight loss interventions before IVF and live births was uncertain, although there was moderate certainty of no association with pregnancy loss.

The findings suggest that weight loss interventions before IVF increase total pregnancies, mainly through an increase in unassisted pregnancy rates. However, further high-quality clinical trials testing different weight loss interventions, particularly those known to achieve greatest weight losses (e.g. low-energy total diet replacement programs) are needed.

Reference:

Moscho Michalopoulou, Susan Ann Jebb, Alice Hobson, et al. The Effect of Weight Loss Before In Vitro Fertilization on Reproductive Outcomes in Women With Obesity: A Systematic Review and Meta-analysis. Ann Intern Med. [Epub 12 August 2025]. doi:10.7326/ANNALS-24-01025.

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Double Relief: Study evaluates Synergistic Effects of Hydromorphone and Ropivacaine in Thoracoscopic Surgery

Recently published clinical trial aimed to evaluate the efficacy of hydromorphone as an adjunct to ropivacaine in serratus anterior plane block (SAPB) for postoperative analgesia and inflammatory response management in patients undergoing video-assisted thoracoscopic surgery (VATS).

Methodology

Patients aged 20-75 with American Society of Anesthesiologists classification I or II were randomized into three groups: Hydromorphone-Ropivacaine SAPB (HR), Ropivacaine SAPB (R), and control (C). Randomization used Excel-generated integers, ensuring blinding throughout the study. A total of 129 patients were identified, with 120 included in the final analysis. VAS scores were recorded at 2, 6, 12, 24, and 48 hours post-surgery, while inflammatory markers (CRP, IL-6, TNF-α) were measured preoperatively and at 24 and 48 hours post-surgery.

Key Findings

Postoperative Pain Relief: Group HR exhibited significantly lower VAS scores than Group C at all measured intervals, particularly at 6 hours post-surgery, where it scored 2.00 (IQR: 2.00) compared to Group C’s 3.00 (IQR: 3.00) (P < 0.001). The HR group showed enhanced pain control throughout the recovery period.

Opioid Consumption: Total opioid consumption and the need for rescue analgesia were significantly reduced in Groups R and HR when compared to Group C. Specifically, HR group had a lower requirement for patient-controlled intravenous analgesia (PCIA) activations (P < 0.001).

Inflammatory Response: The combination of hydromorphone and ropivacaine significantly attenuated postoperative inflammatory markers, with CRP levels being markedly lower in Group HR at 24 and 48 hours compared to Group C (P < 0.001).

Hemodynamic Stability: No significant intraoperative hemodynamic disturbances were attributed to the analgesic techniques, and major postoperative complications were absent.

Limitations

The study was conducted at a single center, potentially limiting the generalizability of findings. Long-term follow-up data was not collected, leaving the long-term effects of the hydromorphone-ropivacaine combination uncertain. Further investigation is needed to compare SAPB with traditional analgesic methods like thoracic epidural analgesia.

Conclusion

The addition of hydromorphone to ropivacaine in SAPB markedly improved postoperative pain management and reduced inflammatory responses in patients undergoing VATS, reinforcing its potential as an effective analgesic strategy. Future research should explore the long-term outcomes and optimal dosing strategies for hydromorphone in SAPB.

Key Points

Analgesic Efficacy: The combination of hydromorphone and ropivacaine in serratus anterior plane block (SAPB) resulted in significantly lower Visual Analog Scale (VAS) pain scores at all assessed time intervals compared to the control group, with the most notable improvement observed at 6 hours post-surgery.

Reduced Opioid Use: Patients receiving the hydromorphone-ropivacaine combination demonstrated a statistically significant reduction in total opioid consumption and need for rescue analgesia, specifically showing fewer activations of patient-controlled intravenous analgesia (PCIA) compared to the control group.

Inflammatory Marker Reduction: The treatment group receiving hydromorphone and ropivacaine showed a marked decrease in inflammatory markers, such as C-reactive protein (CRP), at 24 and 48 hours post-surgery, indicating an enhanced anti-inflammatory response.

Safety Profile: The analgesic techniques employed did not result in significant intraoperative hemodynamic disturbances, and no major postoperative complications were reported, suggesting a favorable safety profile for the combination therapy.

Study Limitations: Generalizability may be constrained as the trial was conducted at a single center, and the absence of long-term follow-up data raises questions about the sustained effects of the hydromorphone-ropivacaine combination.

Future Research Directions: Further studies are recommended to assess long-term outcomes associated with hydromorphone in SAPB and to investigate optimal dosing strategies while potentially comparing SAPB with established analgesic methods such as thoracic epidural analgesia.

Reference –

Xuefeng Chen et al. (2025). The Impact Of Hydromorphone Combined With Ropivacaine In Serratus Anterior Plane Block On Postoperative Pain In Patients Undergoing Video-Assisted Thoracoscopic Pulmonary Lobectomy: A Randomized, Double-Blind Clinical Trial. *BMC Anesthesiology*, 25. https://doi.org/10.1186/s12871-025-03101-2.

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A Gentle Approach: Study Evaluates Efficacy of Medical Management for Missed Miscarriage

Recent study evaluates the efficacy of mifepristone and misoprostol as a medical management option for missed miscarriage, aiming to identify significant risk factors affecting treatment success. Missed miscarriage, identified when a nonviable pregnancy is retained in the uterus, commonly leads to management via expectant, medical, or surgical means, with medical management increasingly favored for its safety and cost-effectiveness.

Research Methodology

The retrospective case-control study analyzed 163 patients diagnosed with missed miscarriage, employing logistic regression to isolate factors influencing treatment success. The primary outcome was the spontaneous passage of the gestational sac within 24 hours of administering misoprostol, emphasizing the efficiency of the medical regimen.

Key Findings

Findings indicate several demographic and clinical variables significantly correlate with medication management outcomes. High gravidity (more than three pregnancies) increased the likelihood of unsuccessful treatment by 3.67 times, while a history of parity and prior miscarriage escalated risks by 2.29 times and 2.09 times, respectively. Additionally, prior uterine surgery, particularly cesarean sections, was associated with a 2.94-fold increase in unsuccessful management. Importantly, the necessity for additional misoprostol doses did not improve success rates, suggesting that the administration dosage may not be the central determinant of efficacy.

Environmental Factors

Meteorological factors were also assessed, revealing that average visibility over four days was linked to treatment outcomes, stressing an intriguing interplay between environmental conditions and medical efficacy. Initial univariable regressions flagged visibility as statistically significant, which multivariable analysis later affirmed as independent of gestational age, reinforcing the need for personalized treatment considerations.

Discussion of Efficacy

Despite mifepristone and misoprostol’s reported efficacy, with previous literature indicating success rates of 83% to 93.3%, results found significant variability due to varying clinical factors. The study posits that not only previous obstetric history but also environmental exposure may influence uterine responsiveness, suggesting further exploration is warranted in broader populations.

Limitations and Future Research

Limitations include the retrospective nature of the study and the potential exclusion of other relevant factors like socioeconomic status and individual lifestyle variables that could confound results. Recommendations for future research emphasize the necessity of prospective multicenter trials with larger sample sizes to validate these findings, aiming toward enhancing clinical guidelines to optimize individualized management strategies for patients facing missed miscarriage.

Key Points

– -Efficacy of Medical Management-: The study assesses mifepristone and misoprostol as a medical management approach for missed miscarriage, favorably contrasted against expectant and surgical methods, emphasizing their safety profile and cost-effectiveness when managing nonviable pregnancies retained in the uterus.

– -Demographic and Clinical Correlates-: Logistic regression analysis on 163 diagnosed cases identified significant risk factors that negatively impacted treatment outcomes, including high gravidity (>3 pregnancies), history of parity, and prior miscarriage, increasing unsuccessful treatment probabilities by 3.67, 2.29, and 2.09 times, respectively. Additionally, prior uterine surgeries, notably cesarean sections, raised the odds of unsuccessful management by 2.94 times.

– -Efficacy of Misoprostol Dosage-: The requirement for additional doses of misoprostol was not associated with improved success rates, challenging the assumption that dosage quantity is the principal factor affecting the efficiency of the medical regimen for missed miscarriage.

– -Influence of Environmental Conditions-: Analysis of environmental factors, specifically average visibility over a four-day period, was shown to correlate with treatment outcomes, suggesting a previously unexamined interaction between meteorological conditions and uterine response to medical management.

– -Variability in Success Rates-: Despite documented success rates of mifepristone and misoprostol ranging from 83% to 93.3%, significant variability was observed based on the demographic and clinical characteristics of the patients, indicating that individualized treatment protocols may be necessary to improve efficacy.

– -Study Limitations and Research Directions-: The retrospective nature limits data interpretation and possible confounding effects of omitted variables such as socioeconomic status and lifestyle. Future research should focus on prospective multicenter trials with larger populations to further corroborate the findings and refine clinical guidelines for the management of missed miscarriage.

Reference –

Huiyuan Wang et al. (2025). Factors Related To Successful Medication Management With Mifepristone And Misoprostol In Missed Miscarriage: A Retrospective Case-Control Study. *BMC Pregnancy And Childbirth*, 25. https://doi.org/10.1186/s12884-025-07662-5.

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IPC 304 A only applicable when doctors commit rash or negligent act: HC relief to doctor

Ernakulam: Quashing the criminal proceedings against a doctor under Section 304 A of the Indian Penal Code, 1860, the Kerala High Court recently observed that a medical practitioner would only be liable under this section if he had committed a rash or negligent act that resulted in the patient’s death.

“The law is thus well laid down that a medical practitioner can be prosecuted for medical negligence only if the procedure/treatment adopted by him is contrary to the general and approved practice. Moreover, for attracting the offence under Section 304A, the doctor should have committed a rash or negligent act,” observed the HC bench comprising Justice V.G. Arun.

“Here it is essential to note that, as far as rash acts are concerned, the criminality lies in running the risk of doing such an act with recklessness or indifference as to the consequences. Criminal negligence on the other hand is the gross and culpable neglect or failure to exercise that reasonable and proper care and precaution to guard against injury, either to the public generally or to an individual in particular which, having regard to all the circumstances out of which the charge has arisen, it was the imperative duty of the accused to have adopted. For attracting the offence under Section 304A, the death must also be the direct or proximate result of the rash or negligent act of the accused,” it further noted.

The plea was filed by the accused, an on-call Medical Officer, seeking quashment of criminal proceedings for medical negligence. The matter concerned a remand prisoner who suffered head injuries after a fall back in January 2021. Even though initially he was treated at local hospitals, due to a lack of beds, he was referred to the Government Medical College Hospital, Kottayam. 

After he suffered another seizure, the patient was referred for a neurosurgery consultation, and the Senior Resident examined him and informed the accused doctor about his condition over the phone. The accused doctor advised a CT scan and pre-operative investigations to be prepared for an emergency surgery.

The next day, when the accused’s duty ended at 8:00 a.m., another doctor (co-accused) assumed the charge as the on-call Medical Officer. It was alleged that even though an emergency surgery was advised after the worsening scan results, the procedure was delayed due to the unavailability of the operating theatre. The patient died in the afternoon on the same day, while awaiting surgery.

Consequently, an FIR was registered, and the patient’s death led to public protests alleging custodial torture, promoting a Crime Branch investigation. An Expert Panel was constituted to investigate the complaints against the doctors, and the panel concluded that the patient had not received reasonable medical care while undergoing the treatment. Accordingly, the accused doctors were booked under Section 304 A IPC.

Challenging this, the petitioner doctor filed the plea before the High Court. The accused’s counsel contended that even if the prosecution allegations were accepted, the offence under Section 304-A IPC would not be attracted because the golden hour, as far as a person with seizure was concerned, was six hours and the inordinate delay in providing proper treatment and medication worsened the patient’s condition.

It was argued that by the time the accused doctor was informed about the patient, already 18 hours had elapsed after the first CT-scan, and it was also the peak pandemic period, and the Government advisories prevented the accused from examining the patient physically. Further, the counsel submitted that in the appeal filed by the accused against the Expert Panel Report, the State Level Apex Expert Committee held that there was no gross and culpable negligence by the doctors at the Medical College in giving treatment to the patient.

On the other hand, the Public Prosecutor submitted that the matter was still being investigated and the investigating officer was not bound by the Apex Body’s findings. Therefore, if there were sufficient materials to prove the accused’s complicity, he could be prosecuted for the alleged offence.

While considering the matter, the HC bench opined that while negligence was an omission to do something which a reasonable man, guided upon those considerations which ordinarily regulated the conduct of human affairs, would do, or the doing of something which a prudent and reasonable man would not do, medical negligence occurred when a doctor breached his duty of care, causing harm to a patient.

The HC bench referred to the Supreme Court order in the case of Suresh Gupta (Dr.) v. Govt. of NCT of Delhi, where the Apex Court had held that “for fixing criminal liability on a doctor or a surgeon, the standard of negligence required to be proved must be so high as can be described as ‘gross negligence’ or ‘recklessness’. It was not merely lack of necessary care, attention and skill.”

The findings in the case of Suresh Gupta were affirmed by the Apex Court in the case of Jacob Mathew v. State of Punjab, where the Court observed that “A simple lack of care, an error of judgment or an accident, is not proof of negligence on the part of a medical professional. So long as a doctor follows a practice acceptable to the medical profession of that day, he cannot be held liable for negligence merely because a better alternative course or method of treatment was also available or simply because a more skilled doctor would not have chosen to follow or resort to that practice or procedure which the accused followed. When it comes to the failure of taking precautions, what has to be seen is whether those precautions were taken which the ordinary experience of men has found to be sufficient; a failure to use special or extraordinary precautions which might have prevented the particular happening cannot be the standard for judging the alleged negligence.”

Further referring to other judicial precedent, the HC bench observed that a medical practitioner can be prosecuted for medical negligence only if the procedure/treatment adopted by him is contrary to the general and approved practice. Moreover, for attracting the offence under Section 304A, the doctor should have committed a rash or negligent act.

The HC bench observed that in this case, the allegation against the petitioner doctor was about the failure to provide timely treatment.

 “Indisputably, there was delay in bringing the patient to the Medical College Hospital after the first seizure. Even after admitting the patient, petitioner was informed about his condition only by 05:20 am on 13.01.2021. Immediately the petitioner directed to conduct CT scan, since no decision could be taken based on the earlier CT scan, which was conducted many hours back and when the patient was in a much better condition. The CT scan report was received at 07:45 am and the petitioner advised for immediate surgery. The petitioner cannot also be attributed with gross negligence for his failure to examine the patient physically since the Covid related SoPs prevented such examination. Further, the petitioner’s duty time ended by 8 am and the delay in conducting the surgery occurred due to nonavailability of operation theatre. Pertinent in this context to note that the Expert Panel had only opined that the patient had not received reasonable standard of care while under treatment in Government Medical College, Kottayam, without naming any particular doctor. Even that opinion of the Expert Panel has lost its relevance in view of the conclusive unanimous opinion of the State Level Apex Body that there was no gross and culpable negligence from the part of the treating doctors for giving treatment to *** (patient).”

Accordingly, the bench observed that the criminal proceedings against the accused doctor were liable to be quashed. It stated,

“In the light of the above undisputed facts, and in view of the law laid down by the Apex Court, it can unhesitatingly be held that the prosecution of the petitioner for the offence under Section 304A amounts to an abuse of process of court. As held by the Supreme Court in State of Haryana and Others v. Bhajan Lal and Others [1992 SCC (Cri) 426], an FIR is liable to be quashed when the allegations, even if accepted in their entirety, do not make out the ingredients for constituting the offence alleged against the accused.”

“For the aforementioned reasons, the Crl.M.C is allowed. FIR and all further proceedings against the petitioner in Crime No.10 of 2021 of the Crime Branch, CU-II Unit, Ernakulam are quashed,” the HC bench further noted.

To view the order, click on the link below:

https://medicaldialogues.in/pdf_upload/kerala-hc-ipc-304-a-298145.pdf

Also Read: Some doctors disregard human life, maligning noble profession: HC refuses to quash FIR under IPC 304A against Specialist

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Favourable Outcomes are reported after Patellofemoral Arthroplasty with the Arthrex iBalance – A Third Generation Implant: study

Patellofemoral arthroplasty (PFA) is an attractive option for patients who have isolated patellofemoral disease with the goal of reproducing normal joint function and kinematics while relieving pain, preserving the tibiofemoral joint, and providing longevity.

Outcomes of many different implants and techniques, ranging from first-generation inlay design, to second-generation on lay design and now robotic or navigated techniques, have been described in the literature with mixed results.

Elizabeth C. Bond et al conducted a study to assess the functional outcomes and revision rates of primary PFA with a third-generation implant with short- to medium-term follow-up.

The authors retrospectively reviewed the records of 49 patients (70 knees) undergoing PFA with the iBalance system by a single surgeon at a quaternary center for demographic and surgical data, as well as complications and revision rates. Patient-reported outcome scores were then collected.

Key findings of the study were:

• The population was majority female (81.6%) with a median age of 50 years.

• Four knees were revised to a total knee arthroplasty (5.7%) at an average time point of 2.3 years postoperatively (range: 1.3-3.5 years).

• The median Single Assessment Numeric Evaluation score at the time of follow-up was 82.5, while the median Kujala score was 72.

• Lower preoperative Kellgren-Lawrence grade was significantly associated with lower Knee Injury and Osteoarthritis Outcome Scores in all 5 domains (P < .05 for all).

• Additional procedures were required in 17 knees (24.3%), in most cases to improve patella tracking.

The authors concluded – “This study is, to our knowledge, the first to examine the short term outcome of the iBalance PFA system. The results show favorable PROs in this group consistent with other 2nd and 3rd generation PFA implants along with a revision rate similar to its prosthetic peers. We plan to continue following our patients in order to report longer-term outcomes of this system.” 

Further reading:

Outcomes After Patellofemoral Arthroplasty with the Arthrex iBalance – A Third Generation Implant Elizabeth C. Bond et al Arthroplasty Today 33 (2025) 101666 https://doi.org/10.1016/j.artd.2025.101666

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HCQ Shows Promise in Reducing Proteinuria in Primary Glomerular Diseases: Study

A new study published in BMC Nephrology found that hydroxychloroquine (HCQ) therapy demonstrated a trend toward reducing proteinuria in patients with primary glomerular diseases. Importantly, HCQ did not significantly impact estimated glomerular filtration rate (eGFR), indicating preserved kidney function during treatment. The study also highlighted HCQ’s favorable safety profile, making it a promising adjunct therapy in managing proteinuria in these patients.

Proteinuria is a key marker of kidney damage in glomerular diseases and is linked to progression to chronic kidney failure. Conventional treatments often involve immunosuppressants with variable efficacy and potential adverse effects. The potential role of HCQ, traditionally used in autoimmune conditions, offers an alternative pathway targeting inflammatory and immunological mechanisms involved in glomerular injury.

While the reduction in proteinuria was a trend rather than statistically definitive, the findings encourage further clinical trials to clarify HCQ’s efficacy and long-term impact on kidney outcomes. The favorable safety observed in this study supports continued exploration of HCQ as a low-risk therapeutic option in nephrology.

Reference:
BMC Nephrology. (2025). Hydroxychloroquine therapy and proteinuria in primary glomerular diseases. https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-025-042XX-X [API]

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D-LECS Shows Promise Over endoscopic resection with Fewer Complications, Finds Study

Japan: Researchers have found in a new study that duodenal laparoscopyendoscopy cooperative surgery is a promising procedure offering better outcomes and a lower complication rate compared to endoscopic resection (ER). However, its indications and feasibility should be evaluated on a case-by-case basis.

The study, published in the Asian Journal of Endoscopic Surgery by Dr. Koji Shindo and colleagues from the Department of Surgery and Oncology at Kyushu University, Japan, aimed to assess the safety and viability of duodenal laparoscopy-endoscopy cooperative surgery (D-LECS). The team compared its short-term outcomes with those of traditional ER techniques in patients with duodenal tumors, focusing on complication rates and oncological efficacy.

The retrospective single-center study analyzed data from 30 patients treated between March 2013 and March 2023. Of these, 15 patients underwent D-LECS, while the remaining 15 received ER, which included endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), or a hybrid ESD approach. In two ER cases, procedures were observed laparoscopically without any intervention such as suturing.

The study revealed the following findings:

  • Two patients in the D-LECS group required conversion to open surgery to avoid potential injury to the ampulla of Vater.
  • The overall operation time was significantly longer for the D-LECS group.
  • Endoscopy time was similar between the D-LECS and ER groups.
  • The length of postoperative hospital stay was comparable in both groups.
  • The ER group had a significantly higher rate of moderate-to-severe complications (Clavien–Dindo grade II or higher) compared to the D-LECS group.
  • Piecemeal resections and positive resection margins were observed in both groups, with no significant difference.
  • One patient in each group experienced tumor recurrence.
  • In the D-LECS group, one patient with positive resection margins who refused additional surgery later died of duodenal cancer.

The findings highlight the potential benefits of D-LECS in managing duodenal tumors, especially in terms of safety and procedural outcomes. However, the authors emphasize the importance of individualized evaluation to determine whether D-LECS is suitable for each patient, as factors such as tumor location and risk of complications must be considered.

“Overall, the study supports D-LECS as an effective alternative to ER, offering improved safety without compromising oncological outcomes, and highlights the need for further research to refine patient selection criteria,” the authors concluded.

Reference:

Shindo, K., Ohuchida, K., Nagasue, T., Ogino, H., Horioka, K., Moriyama, T., Nagayoshi, K., Mizuuchi, Y., Ikenaga, N., Nakata, K., Oda, Y., & Nakamura, M. (2024). Efficacy of Laparoscopic and Endoscopic Cooperative Surgery Compared to Endoscopic Resection for Duodenal Tumor Treatment. Asian Journal of Endoscopic Surgery, 18(1), e70130. https://doi.org/10.1111/ases.70130

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Hyperbaric Oxygen Therapy Enhances Hearing Recovery in Sudden Sensorineural Hearing Loss Patients: Study

Researchers found that the application of hyperbaric oxygen therapy (HBOT) in addition to current medical treatment significantly improves hearing gain in the case of sudden sensorineural hearing loss (SSNHL). SSNHL, an acute hearing impairment happening in thousands of individuals each year, is a challenging condition with unclear pathogenesis and variable responsiveness to treatment. The study was recently published in the journal Laryngoscope by Issac L. and colleagues.

Systematic review entailed extensive search on major databases, such as PubMed, EMBASE, CENTRAL, MEDLINE, Google Scholar, Web of Science, and ClinicalTrials.gov, for publications up to May 7, 2025. The review was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Two independent reviewers screened and selected eligible studies and extracted data. Meta-analysis was conducted using a random-effects model to combine odds ratios (ORs) for recovery of hearing.

The review consisted of 20 studies, including 16 randomized controlled trials (RCTs) and four prospective non-randomized studies. A total of 1,087 patients who underwent HBOT and 600 medical therapy alone-treated patients were assessed.

Key Findings

• The meta-analysis consisted of ten studies and demonstrated convincing evidence favoring the application of HBOT in conjunction with MT alone, including steroids.

• Patients treated with HBOT and medical therapy had 2.61 times greater chances of hearing improvement compared to those treated with medical therapy only (OR 2.61, 95% CI 1.86–3.68, p < 0.001).

• Subgroup analysis between HBOT + systemic steroids (SS) and SS alone revealed HBOT was linked with better outcomes (OR 2.54, 95% CI 1.63–3.97, p < 0.001).

• When HBOT + SS + intratympanic steroids (ITS) was contrasted with SS + ITS alone, the probability of recovery of hearing was still significantly higher for the HBOT group (OR 2.64, 95% CI 1.39–5.02, p < 0.001).

• It is highly suggestive of the fact that HBOT improves the effectiveness of both systemic and intratympanic steroid therapy for SSNHL.

This meta-analysis and systematic review came to the conclusion that standard medical therapy supplemented with hyperbaric oxygen therapy significantly enhances hearing outcomes in patients with sudden sensorineural hearing loss. These findings support the inclusion of HBOT in the treatment protocol in suitable patients.

Reference:

Alter, I. L., Hamiter, M., Han, J., Leu, C. S., Usseglio, J., & Lalwani, A. K. (2025). Hyperbaric Oxygen and Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis. The Laryngoscope, 10.1002/lary.32472. Advance online publication. https://doi.org/10.1002/lary.32472

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Tildrakizumab Shows Significant Efficacy in Psoriatic Arthritis Phase 3 Trials

Phase 3 trials have demonstrated that tildrakizumab 100mg significantly improved ACR20 response rates in patients with active psoriatic arthritis at 24 weeks compared to placebo, marking a promising advancement in PsA treatment.

Treatment with tildrakizumab 100 mg (ILUMYA) resulted in greater improvements in PsA signs and symptoms at
Week 24 compared to treatment with placebo. Both the INSPIRE-1 and INSPIRE-2 studies achieved the primary
endpoint, with a higher proportion of patients in the INSPIRE-1 and INSPIRE-2 studies treated with tildrakizumab
achieving ACR20 responses at week 24, compared to those receiving placebo (p < 0.05).


“We are excited to share that both the INSPIRE-1 and INSPIRE-2 clinical trials have successfully met their primary
endpoints. These top-line results reinforce the therapeutic potential of ILUMYA as a treatment option for patients
with active psoriatic arthritis. We extend our sincere gratitude to the patients, healthcare professionals and
administrators whose contributions made the studies possible. We look forward to sharing the complete clinical data
in the near future,” said Marek Honczarenko, MD, PhD, Senior Vice President and Head of Global Specialty
Development at Sun Pharma.

Safety data in the studies was consistent with the well-documented safety profile of ILUMYA, which is approved for
the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or
phototherapy. No new safety signals were identified in the INSPIRE-1 and INSPIRE-2 studies.

Findings from the INSPIRE studies will be presented at upcoming medical conferences and published in a peerreviewed medical journal. Use of tildrakizumab 100 mg (ILUMYA) in psoriatic arthritis is not approved, and its
safety and efficacy have not been evaluated by regulatory authorities.

About the INSPIRE-1 and INSPIRE-2 Phase 3 studies

The INSPIRE-1 and INSPIRE-2 are both 52-week global, multicenter, randomized, double-blind, single-dose,
placebo-controlled Phase 3 studies aimed at assessing the efficacy and safety of tildrakizumab 100 mg (ILUMYA®)
in adult patients with active psoriatic arthritis. The INSPIRE-1 enrolled patients having prior exposure to an antiTNF agent while the INSPIRE-2 enrolled anti-TNF naïve patients. A total of over 800 adult patients were enrolled
for the two studies from clinical sites in the US, Europe and Asia. Patients were randomized to receive either
tildrakizumab 100 mg (ILUMYA®) or placebo.
An induction dose was not administered in either study. Study
participants were permitted to use concomitant methotrexate or leflunomide, provided the dose remained stable
throughout the trial. In the INSPIRE-1 and INSPIRE-2 studies, tildrakizumab 100 mg (ILUMYA®) was administered
at Week 0 and then every 12 weeks. In contrast, in Phase 3 studies for chronic plaque psoriasis, the treatment schedule
included doses in Week 0, Week 4, and then every 12 weeks thereafter. ILUMYA® is approved by the regulatory
Agencies for the indication of chronic plaques psoriasis.
The primary endpoint for both studies is the proportion of participants achieving an ACR20 response at Week 24.
The key secondary efficacy endpoints at 24 weeks include ACR50, ACR70, and PASI75 and improvement. Learn
more about the studies at clinicaltrials.gov (INSPIRE-1 NCT04314544 and INSPIRE-2 NCT04314531).
The ACR20 is a composite measure defined as a 20 percent improvement in both the number of tender and number
of swollen joints and a 20 percent improvement in three of the following five criteria: patient global assessment,
physician global assessment, functional ability measure (most often HAQ-DI), visual analog pain scale, and
erythrocyte sedimentation rate or C-reactive protein (CRP). ACR50 and ACR70 are the same measurement with
improvement levels of 50 percent and 70 percent, respectively.

About Psoriatic Arthritis (PsA)

Psoriatic arthritis (PsA) is a chronic (long-lasting or recurring) disease related to the immune system. It causes
swelling, pain, and stiffness in joints and entheses (places where tendons and ligaments connect to bones). Psoriatic
arthritis can develop at any age. Psoriatic arthritis can occur regardless of the severity of psoriasis (mild, moderate,
or severe). Roughly 1 in 3 people living with psoriasis also have psoriatic arthritis [3]; typically, with psoriasis
developing before psoriatic arthritis. While as many as 2.4 million Americans live with psoriatic arthritis, more
than 15% of people living with psoriasis may also have undiagnosed psoriatic arthritis.

About ILUMYA® (tildrakizumab-asmn)

ILUMYA (tildrakizumab-asmn) is a humanized lgG1/k monoclonal antibody designed to selectively bind to the p19
subunit of interleukin-23 (IL-23) and inhibit its interaction with the IL-23 receptor, leading to inhibition of the release
of pro-inflammatory cytokines and chemokines. ILUMYA is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy, in the United States and other countries.

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Mfn2 and Preeclampsia: Study Exploring a Potential Game Changer in Maternal Health: Study

Recent study investigates the expression of mitofusin 2 (Mfn2) in placentas and peripheral blood from patients with early-onset preeclampsia (eoPE) and late-onset preeclampsia (loPE), exploring its potential as a diagnostic and therapeutic target for preeclampsia. Preeclampsia, a serious condition occurring after 20 weeks of gestation, presents significant morbidity and mortality risks, particularly differentiating between eoPE (before 34 weeks) and loPE (after 34 weeks) due to varying placental and maternal pathophysiologies.

Role of Mfn2 in Preeclampsia

Mfn2, a mitochondrial outer membrane protein critical for mitochondrial dynamics, was previously noted to be downregulated in preeclampsia, associated with increased apoptosis and mitochondrial dysfunction. The study emphasizes the differences in placental pathology between eoPE and loPE, highlighting impaired remodeling of uterine spiral arteries in eoPE, leading to ischemia and hypoxia. In contrast, loPE presents with maintained or higher placental perfusion levels.

Mfn2 Expression Analysis

Quantitative assessments revealed a significant decrease in Mfn2 mRNA levels in placentas from eoPE patients compared to both loPE and normal control groups, while loPE did not show significant downregulation compared to controls. Peripheral blood analyses indicated higher levels of Mfn2 protein in both preeclampsia groups compared to controls, with eoPE showing the highest levels. Notably, Mfn2 levels were positively correlated with the severity of preeclampsia, such as systolic and diastolic blood pressure and proteinuria, with stronger correlations in eoPE. The findings suggest a stratification in the role of Mfn2 between the two conditions, establishing that the reduction of Mfn2 in eoPE is indicative of significant mitochondrial dysfunction, while the elevated serum levels in both preeclampsia types may reflect a compensatory response to placental mitochondrial damage. Moreover, these elevated Mfn2 levels were negatively correlated with birth weight and Apgar scores, indicating poor pregnancy outcomes associated with elevated Mfn2 levels.

Conclusion and Future Directions

In summary, this investigation highlights Mfn2’s potential as a biomarker for preeclampsia severity and progression, distinguishing the distinct roles of mitochondrial dysfunction in eoPE and loPE. The findings support the hypothesis that early identification of impaired Mfn2 expression could facilitate enhanced diagnostic and therapeutic strategies for preeclampsia management, advocating for further research to validate these findings in larger cohorts and longitudinal studies.

Key Points

– -Expression Analysis of Mfn2-: Significant downregulation of Mfn2 mRNA levels was identified in placentas from patients with early-onset preeclampsia (eoPE) when compared to both late-onset preeclampsia (loPE) and normal control samples, while loPE did not exhibit significant differences in Mfn2 levels compared to controls.

– -Peripheral Blood Findings-: Elevated Mfn2 protein levels were observed in peripheral blood from both eoPE and loPE patients compared to controls, with eoPE showing the highest serum Mfn2 levels. This suggests a potential compensatory mechanism in response to placental mitochondrial damage.

– -Correlation with Disease Severity-: Mfn2 levels exhibited positive correlations with the severity of preeclampsia indicators such as systolic and diastolic blood pressure, as well as proteinuria. These correlations were found to be more robust in the eoPE cohort, indicating that altered Mfn2 expression may reflect the severity of the condition.

– -Implications for Pregnancy Outcomes-: Elevated Mfn2 levels in both types of preeclampsia were negatively correlated with birth weight and Apgar scores, suggesting that higher Mfn2 may be associated with adverse pregnancy outcomes and poorer fetal health.

– -Differentiation of Pathophysiology-: The study emphasizes the divergent mechanisms of placental pathology between eoPE and loPE, with eoPE characterized by impaired remodeling of uterine spiral arteries, leading to ischemic conditions, whereas loPE maintains or improves placental perfusion levels.

– -Future Research Directions-: The findings propose Mfn2 as a potential biomarker for assessing preeclampsia severity and progression, underscoring the need for further investigations in larger cohorts and longitudinal studies to validate Mfn2’s utility in diagnostic and therapeutic approaches for preeclampsia.

Reference –

Dandan Sun et al. (2025). A Mitochondrial Regulator Protein, Mitofusin 2, Is Elevated In The Maternal Blood Of Women With Preeclampsia. *BMC Pregnancy And Childbirth*, 25. https://doi.org/10.1186/s12884-025-07663-4.

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